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Clinical Trial Results:
A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with moderate to severe rheumatoid arthritis

Summary
EudraCT number	2016-000912-13
Trial protocol	DE ES PL GB
Global end of trial date	22 Oct 2018

Results information
Results version number	v1(current)
This version publication date	28 Oct 2019
First version publication date	28 Oct 2019
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

203168

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

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

21 Feb 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Oct 2018

Was the trial ended prematurely?

Main objective of the trial

To investigate the safety and tolerability of GSK2982772 in subjects with moderate to severe Rheumatoid Arthritis

Protection of trial subjects

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Oct 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 7

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Poland: 26

Country: Number of subjects enrolled

Russian Federation: 9

Country: Number of subjects enrolled

Spain: 7

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

The study evaluated safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of GSK2982772 in participants with rheumatoid arthritis (RA). Participants were randomly assigned to receive either GSK2982772 60 milligram (mg) or placebo to be taken orally twice daily (BID) or three times daily (TID) for 84 days.

Screening details

A total of 99 participants were screened, of them, 47 participants were screen failures and 52 participants were enrolled. Of them, 51 participants received study treatment. One participant was enrolled in the study but never received study treatment as eligibility criteria for dose was not met.

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

Are arms mutually exclusive

Yes

Placebo BID

Arm description

Participants received placebo orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

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

Two tablets taken orally BID.

Placebo TID

Arm description

Participants received placebo orally three times daily (TID) (approximately 8 hours apart) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

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

Two tablets taken orally TID.

GSK2982772 60 mg BID

Arm description

Participants received GSK2982772 orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Arm type

Experimental

Investigational medicinal product name

GSK2982772

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two tablets (30 mg) taken orally BID.

GSK2982772 60 mg TID

Arm description

Participants received GSK2982772 orally three times daily (TID) (approximately 8 hours apart) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Arm type

Experimental

Investigational medicinal product name

GSK2982772

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two tablets (30 mg) taken orally TID.

Number of subjects in period 1 ^[1]	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Started	3	15	5	28
Completed	3	14	5	22
Not completed	0	1	0	6
Consent withdrawn by subject	-	1	-	1
Adverse event, non-fatal	-	-	-	3
Protocol defined stopping criteria	-	-	-	1
Lack of efficacy	-	-	-	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: A total of 52 participants were enrolled. Of them, 51 participants received study treatment. One participant was enrolled in the study but never received study treatment as eligibility criteria for dose was not met.

Baseline characteristics

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Reporting group title

Placebo BID

Reporting group description

Participants received placebo orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Reporting group title

Placebo TID

Reporting group description

Reporting group title

GSK2982772 60 mg BID

Reporting group description

Participants received GSK2982772 orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Reporting group title

GSK2982772 60 mg TID

Reporting group description

Reporting group values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID	Total
Number of subjects	3	15	5	28	51
Age categorical
Units: Subjects
Total participants	3	15	5	28	51
Age Continuous
Units: Years
arithmetic mean (standard deviation)	53.3 ± 4.93	53.1 ± 7.80	53.6 ± 7.86	55.0 ± 11.25	-
Sex: Female, Male
Units: Subjects
Female	2	13	4	23	42
Male	1	2	1	5	9
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaskan Native	0	0	0	1	1
White-White/Caucasian/European Heritage	3	15	5	27	50

End points

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Reporting group title

Placebo BID

Reporting group description

Participants received placebo orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Reporting group title

Placebo TID

Reporting group description

Reporting group title

GSK2982772 60 mg BID

Reporting group description

Participants received GSK2982772 orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Reporting group title

GSK2982772 60 mg TID

Reporting group description

Primary: Number of participants with non-serious adverse events (nSAEs) and serious adverse events (SAEs) as a measure of safety and tolerability

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End point title

Number of participants with non-serious adverse events (nSAEs) and serious adverse events (SAEs) as a measure of safety and tolerability ^[1]

End point description

An AE was 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Number of participants with any nSAE or SAE are presented. Safety Population comprised of all participants who received at least one dose of the study treatment.

End point type

Primary

End point timeframe

Up to Day 112

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[2]	15 ^[3]	5 ^[4]	28 ^[5]
Units: Participants
Any nSAEs	3	10	3	16
Any SAEs	0	0	0	2

Notes
[2] - Safety Population
[3] - Safety Population
[4] - Safety Population
[5] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst case clinical chemistry parameters of potential clinical importance (PCI)

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End point title

Number of participants with worst case clinical chemistry parameters of potential clinical importance (PCI) ^[6]

End point description

Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): >=2*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 millimoles per liter(mmol/L), alkaline phosphatase(high): >=2*ULN U/L, AST(high): >=2*ULN U/L, calcium: <2(low) or >2.75 mmol/L(high), creatinine (high): increase from Baseline >44.25 mmol/L, glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and total bilirubin(high): >=1.5*ULN micromoles per liter(µmol/L). Participants were counted in the worst case category if their value changes (to low or to high), unless there is no change in their category. Only those clinical chemistry parameters with PCI values (to low and to high) have been presented.

End point type

Primary

End point timeframe

Up to Day 112

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[7]	15 ^[8]	5 ^[9]	28 ^[10]
Units: Participants
ALT; To low	0	0	0	0
ALT; To high	0	0	0	2
Albumin; To low	0	0	0	0
Albumin; To high	0	0	0	0
Alkaline phosphatase; To Low	0	0	0	0
Alkaline phosphatase; To high	0	0	0	0
AST; To low	0	0	0	0
AST; To high	0	0	0	1
Calcium; To low	0	0	0	0
Calcium; To high	0	0	0	0
Creatinine; To low	0	0	0	0
Creatinine; To high	0	0	0	0
Glucose; To low	0	1	0	0
Glucose; To high	0	1	0	1
Potassium; To low	0	0	0	0
Potassium; To high	0	0	0	1
Sodium; To low	0	0	0	0
Sodium; To high	0	0	0	0
Total bilirubin; To low	0	0	0	0
Total bilirubin; To high	0	0	0	0

Notes
[7] - Safety Population
[8] - Safety Population
[9] - Safety Population
[10] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst case hematology parameters of PCI

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End point title

Number of participants with worst case hematology parameters of PCI ^[11]

End point description

Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs). PCI ranges were < 0.075 (decrease from baseline) or >0.54 proportion of red blood cells in blood (high) for hematocrit, <25 (low) or >180 grams per liter (g/L) (high) for hemoglobin, <0.8 x10^9 cells per liter (cells/L) for lymphocytes (low), <100 (low) or >550 x10^9 cells/L(high) for platelets, <1.5 x10^9 cells/L (low) for total neutrophils and < 3 (low) or >20 x10^9 cells/L (high) for WBCs. Participants were counted in the worst case category that their value changes (to low or to high), unless there is no change in their category. Only those hematology parameters with PCI values (to low and to high) have been presented.

End point type

Primary

End point timeframe

Up to Day 112

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[12]	15 ^[13]	5 ^[14]	28 ^[15]
Units: Participants
Hematocrit; To low	0	0	0	0
Hematocrit; To high	0	0	0	0
Hemoglobin; To low	0	0	0	0
Hemoglobin; To high	0	0	0	0
Lymphocytes; To Low	2	1	0	1
Lymphocytes; To high	0	0	0	0
Platelet count; To low	0	0	0	0
Platelet count; To high	0	0	0	0
Total neutrophils; To low	0	0	0	1
Total neutrophils; To high	0	0	0	0
WBC; To low	0	0	0	1
WBC; To high	0	1	0	0

Notes
[12] - Safety Population
[13] - Safety Population
[14] - Safety Population
[15] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by dipstick method

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End point title

Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by dipstick method ^[16]

End point description

Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Only participants with worst case any increase from Baseline values are presented.

End point type

Primary

End point timeframe

Up to Day 112

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[17]	15 ^[18]	5 ^[19]	28 ^[20]
Units: Participants
Glucose; Any increase	0	0	0	0
Ketones; Any increase	1	3	3	6
Occult blood; Any increase	0	6	1	8
Protein; Any increase	1	2	0	6

Notes
[17] - Safety Population
[18] - Safety Population
[19] - Safety Population
[20] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by microscopy method

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End point title

Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by microscopy method ^[21]

End point description

Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. Microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for hyaline casts, red blood cells and white blood cells. Results for microscopy parameters hyaline casts, red blood cells and white blood cells were categorized as 'any increase from Baseline', which imply any increase in their count in the urine sample. Only participants with worst case any increase from Baseline values are presented. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). 99999 indicates data is not available.

End point type

Primary

End point timeframe

Up to Day 112

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[22]	7 ^[23]	1 ^[24]	11 ^[25]
Units: Participants
Hyaline casts;any increase;n=0,1,0,0	99999	1	99999	99999
Red blood cells;any increase;n=2,7,1,11	1	5	1	8
White blood cells;any increase;n=2,7,1,11	2	5	1	7

Notes
[22] - Safety Population
[23] - Safety Population
[24] - Safety Population
[25] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in electrocardiogram (ECG) heart rate at indicated time points

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End point title

Change from Baseline in electrocardiogram (ECG) heart rate at indicated time points ^[26]

End point description

12- lead ECG was measured on each day using an ECG machine that automatically calculated the heart rate and measured PR interval, QRS duration, QT interval, QT interval corrected for heart rate according to either Bazett's formula (QTcB) and QT interval corrected for heart rate according to Fridericia's formula (QTcF). ECG was measured in semi-supine or supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Primary

End point timeframe

Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[27]	14 ^[28]	5 ^[29]	24 ^[30]
Units: Beats per minute
arithmetic mean (standard deviation)
Day 8; n=3,14,5,23	7.0 ± 5.57	1.1 ± 10.68	0.6 ± 7.09	0.6 ± 7.55
Day 15; n=3,14,5,24	0.7 ± 2.08	-0.3 ± 11.64	-4.6 ± 4.16	1.0 ± 9.94
Day 29; n=3,14,5,22	2.7 ± 4.93	-1.4 ± 8.27	-5.8 ± 13.66	1.3 ± 9.14
Day 43; n=3,13,5,23	-0.7 ± 7.57	-3.5 ± 9.73	-6.0 ± 7.35	-0.2 ± 10.86
Day 57; n=3,13,5,22	-3.7 ± 10.69	-2.4 ± 8.79	-4.2 ± 8.58	0.7 ± 9.75
Day 71; n=3,13,5,22	0.3 ± 9.29	-3.0 ± 12.08	-7.6 ± 7.73	0.3 ± 9.32
Day 85; n=3,13,5,21	-1.7 ± 5.69	-4.1 ± 11.51	-2.4 ± 4.72	-1.4 ± 9.12

Notes
[27] - Safety Population
[28] - Safety Population
[29] - Safety Population
[30] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time points

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End point title

Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time points ^[31]

End point description

12- lead ECG was measured on each day using an ECG machine that automatically calculated the heart rate and measured PR interval, QRS duration, QT interval QTcB and QTcF. ECG was measured in semi-supine or supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Primary

End point timeframe

Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[32]	14 ^[33]	5 ^[34]	24 ^[35]
Units: Millisecond
arithmetic mean (standard deviation)
PR interval; Day 8; n=3,14,5,23	-0.3 ± 14.36	-1.9 ± 26.35	-6.4 ± 19.98	0.8 ± 18.84
PR interval; Day 15; n=3,14,5,24	6.3 ± 12.66	0.6 ± 29.94	-2.0 ± 23.10	3.0 ± 15.71
PR interval; Day 29; n=3,14,5,22	5.3 ± 24.01	-3.5 ± 32.15	-0.2 ± 22.66	-6.9 ± 28.00
PR interval; Day 43; n=3,13,5,23	2.0 ± 17.35	6.5 ± 14.44	2.4 ± 5.41	6.6 ± 15.69
PR interval; Day 57; n=3,13,5,22	-12.0 ± 5.29	5.8 ± 21.75	5.0 ± 6.36	4.1 ± 17.51
PR interval; Day 71; n=3,13,5,22	1.0 ± 17.78	1.2 ± 18.65	2.2 ± 23.92	0.8 ± 15.06
PR interval; Day 85; n=3,13,5,21	1.3 ± 10.02	6.2 ± 15.38	-0.2 ± 5.26	0.4 ± 10.29
QRS duration; Day 8; n=3,14,5,23	-4.7 ± 5.03	-3.3 ± 10.75	8.2 ± 10.33	3.7 ± 12.97
QRS duration; Day 15; n=3,14,5,24	-3.3 ± 4.16	-3.1 ± 10.50	-1.2 ± 7.26	1.1 ± 6.89
QRS duration; Day 29; n=3,14,5,22	-1.3 ± 3.79	-2.1 ± 10.89	0.4 ± 5.03	-0.5 ± 9.01
QRS duration; Day 43; n=3,13,5,23	-3.3 ± 5.51	-1.1 ± 9.90	3.6 ± 8.29	0.3 ± 10.48
QRS duration; Day 57; n=3,13,5,22	-6.0 ± 6.00	-4.0 ± 5.90	3.2 ± 9.34	1.0 ± 18.33
QRS duration; Day 71; n=3,13,5,22	-10.0 ± 7.55	-0.2 ± 6.68	4.6 ± 12.26	-0.5 ± 8.31
QRS duration; Day 85; n=3,13,5,21	-7.3 ± 11.37	-1.0 ± 9.07	3.4 ± 8.68	1.5 ± 10.68
QT interval; Day 8; n=3,14,5,23	-25.7 ± 6.11	6.4 ± 40.17	-14.2 ± 22.49	-1.0 ± 35.97
QT interval; Day 15; n=3,14,5,24	2.7 ± 11.02	20.7 ± 34.85	0.0 ± 21.12	-4.5 ± 25.27
QT interval; Day 29; n=3,14,5,22	-9.3 ± 17.67	7.6 ± 25.03	-5.6 ± 22.37	5.5 ± 31.49
QT interval; Day 43; n=3,13,5,23	-12.7 ± 28.10	18.5 ± 38.73	1.0 ± 20.74	0.6 ± 29.36
QT interval; Day 57; n=3,13,5,22	12.3 ± 30.04	13.6 ± 41.48	2.4 ± 22.78	-1.8 ± 36.44
QT interval; Day 71; n=3,13,5,22	-9.3 ± 33.98	13.8 ± 32.50	10.2 ± 28.71	-2.1 ± 22.06
QT interval; Day 85; n=3,13,5,21	-0.3 ± 14.50	17.2 ± 32.16	-3.2 ± 14.60	3.0 ± 17.28
QTcB; Day 8; n=2,14,5,22	-12.1 ± 8.34	10.5 ± 46.28	-10.3 ± 14.09	0.7 ± 33.20
QTcB; Day 15; n=2,14,5,23	7.2 ± 7.18	22.9 ± 46.10	-12.9 ± 17.59	-0.9 ± 19.63
QTcB; Day 29; n=2,14,5,21	-2.4 ± 7.96	4.4 ± 25.73	-21.2 ± 29.58	10.3 ± 29.02
QTcB; Day 43; n=2,13,5,22	-13.0 ± 14.51	9.1 ± 37.18	-14.2 ± 14.64	0.6 ± 27.77
QTcB; Day 57; n=2,13,5,21	-1.5 ± 1.83	7.5 ± 38.73	-7.0 ± 11.67	1.1 ± 47.85
QTcB; Day 71; n=2,13,5,21	-9.3 ± 16.59	4.6 ± 34.77	-11.0 ± 16.47	-1.1 ± 20.55
QTcB; Day 85; n=2,13,5,20	4.2 ± 15.78	7.0 ± 32.09	-9.1 ± 12.42	-0.7 ± 17.51
QTcF; Day 8; n=2,14,5,22	-16.0 ± 3.35	9.0 ± 42.58	-11.4 ± 14.05	0.3 ± 33.04
QTcF; Day 15; n=2,14,5,23	7.5 ± 7.65	22.2 ± 39.68	-8.4 ± 18.00	-2.3 ± 17.61
QTcF; Day 29; n=2,14,5,21	-3.3 ± 13.16	5.6 ± 22.87	-15.6 ± 18.24	8.7 ± 27.77
QTcF; Day 43; n=2,13,5,22	-13.5 ± 23.40	12.4 ± 35.37	-8.7 ± 13.81	0.7 ± 25.16
QTcF; Day 57; n=2,13,5,21	5.9 ± 11.57	9.6 ± 38.25	-3.5 ± 11.35	-0.1 ± 42.41
QTcF; Day 71; n=2,13,5,21	-11.1 ± 27.30	7.6 ± 30.12	-3.5 ± 18.48	-1.2 ± 17.15
QTcF; Day 85; n=2,13,5,20	2.5 ± 17.46	10.6 ± 28.46	-7.0 ± 11.36	0.6 ± 12.45

Notes
[32] - Safety Population
[33] - Safety Population
[34] - Safety Population
[35] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time points

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End point title

Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time points ^[36]

End point description

SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Primary

End point timeframe

Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85

Notes
[36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[37]	15 ^[38]	5 ^[39]	25 ^[40]
Units: Millimeters of Mercury (mmHg)
arithmetic mean (standard deviation)
SBP; Day 8; n=3,15,5,25	-9.7 ± 5.69	0.5 ± 12.61	-4.6 ± 14.33	2.7 ± 11.0
SBP; Day 15; n=3,15,5,25	-2.0 ± 7.55	-2.7 ± 11.21	-13.0 ± 12.79	4.6 ± 9.43
SBP; Day 29; n=3,15,5,24	-9.3 ± 15.70	-0.8 ± 10.82	-8.2 ± 19.12	1.9 ± 11.94
SBP; Day 43; n=3,14,5,24	-7.0 ± 9.54	-2.0 ± 15.11	-11.4 ± 19.72	-1.6 ± 10.01
SBP; Day 57; n=3,14,5,23	-14.7 ± 17.21	0.5 ± 16.19	-9.6 ± 18.49	-0.3 ± 12.84
SBP; Day 71; n=3,14,5,23	-7.0 ± 9.85	1.1 ± 14.35	-8.2 ± 12.19	1.2 ± 14.40
SBP; Day 85; n=3,14,5,22	-4.3 ± 12.70	-0.1 ± 14.68	-4.8 ± 11.23	1.9 ± 12.97
DBP; Day 8; n=3,15,5,25	2.00 ± 5.00	2.0 ± 11.32	1.0 ± 8.69	-0.4 ± 7.12
DBP; Day 15; n=3,15,5,25	0.3 ± 6.11	0.3 ± 7.85	0.4 ± 4.39	1.1 ± 7.61
DBP; Day 29; n=3,15,5,24	-4.0 ± 8.89	0.2 ± 8.28	-2.0 ± 6.04	0.7 ± 7.65
DBP; Day 43; n=3,14,5,24	0.3 ± 14.36	-0.3 ± 8.96	-1.4 ± 8.76	-0.8 ± 6.68
DBP; Day 57; n=3,14,5,23	-3.7 ± 8.33	0.8 ± 9.90	1.4 ± 6.43	-0.9 ± 7.78
DBP; Day 71; n=3,14,5,23	-7.0 ± 9.17	1.4 ± 8.36	-7.2 ± 9.76	-1.5 ± 6.90
DBP; Day 85; n=3,14,5,22	1.0 ± 6.24	2.1 ± 10.79	-1.4 ± 7.67	-0.4 ± 7.50

Notes
[37] - Safety Population
[38] - Safety Population
[39] - Safety Population
[40] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in respiratory rate at indicated time points

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End point title

Change from Baseline in respiratory rate at indicated time points ^[41]

End point description

Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Primary

End point timeframe

Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[42]	15 ^[43]	5 ^[44]	25 ^[45]
Units: Breaths per minute
arithmetic mean (standard deviation)
Day 8; n=3,15,5,25	0.7 ± 1.53	0.1 ± 1.13	-0.4 ± 2.61	0.0 ± 1.14
Day 15; n=3,15,5,25	1.0 ± 1.73	0.2 ± 1.08	-1.2 ± 1.79	0.2 ± 1.91
Day 29; n=3,15,5,24	1.0 ± 1.00	-0.2 ± 1.47	-1.6 ± 1.67	0.1 ± 1.28
Day 43; n=3,14,5,24	1.7 ± 0.58	0.3 ± 1.33	-0.8 ± 1.10	0.5 ± 2.70
Day 57; n=3,14,5,23	1.7 ± 2.08	0.2 ± 0.70	0.4 ± 3.29	0.6 ± 2.00
Day 71; n=3,14,5,23	1.7 ± 0.58	0.5 ± 0.65	0.0 ± 2.45	0.7 ± 2.07
Day 85; n=3,14,5,22	0.7 ± 0.58	0.4 ± 0.84	-0.4 ± 2.61	0.5 ± 1.60

Notes
[42] - Safety Population
[43] - Safety Population
[44] - Safety Population
[45] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in body temperature at indicated time points

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End point title

Change from Baseline in body temperature at indicated time points ^[46]

End point description

Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Primary

End point timeframe

Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85

Notes
[46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[47]	15 ^[48]	5 ^[49]	25 ^[50]
Units: Degrees Celsius
arithmetic mean (standard deviation)
Day 8; n=3,15,5,25	0.60 ± 0.529	-0.03 ± 0.209	-0.06 ± 0.261	0.06 ± 0.222
Day 15; n=3,15,5,25	0.80 ± 0.500	-0.07 ± 0.171	-0.04 ± 0.219	0.06 ± 0.251
Day 29; n=3,15,5,24	0.60 ± 0.656	-0.02 ± 0.204	0.10 ± 0.187	0.11 ± 0.249
Day 43; n=3,14,5,24	0.53 ± 0.513	-0.01 ± 0.251	0.04 ± 0.270	0.06 ± 0.286
Day 57; n=3,14,5,23	0.53 ± 0.462	-0.02 ± 0.226	-0.02 ± 0.239	0.16 ± 0.310
Day 71; n=3,14,5,23	0.27 ± 0.404	-0.06 ± 0.210	-0.00 ± 0.141	0.17 ± 0.255
Day 85; n=3,14,5,22	0.53 ± 0.379	-0.10 ± 0.162	-0.12 ± 0.356	0.14 ± 0.353

Notes
[47] - Safety Population
[48] - Safety Population
[49] - Safety Population
[50] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in vital sign-heart rate at indicated time points

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End point title

Change from Baseline in vital sign-heart rate at indicated time points ^[51]

End point description

Vital sign-heart rate was planned to be assessed as a measure of safety and tolerability. The data for assessment of vital sign-heart rate was not collected.

End point type

Primary

End point timeframe

Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85

Notes
[51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[52]	0 ^[53]	0 ^[54]	0 ^[55]
Units: Beats per minute
arithmetic mean (standard deviation)	±	±	±	±

Notes
[52] - Safety Population
[53] - Safety Population
[54] - Safety Population
[55] - Safety Population

No statistical analyses for this end point

Secondary: Pre-dose plasma concentrations of GSK2982772 on Days 8 and 43

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End point title

Pre-dose plasma concentrations of GSK2982772 on Days 8 and 43 ^[56]

End point description

Blood samples were collected on Day 8 and Day 43 for determining pre-dose plasma concentrations of GSK2982772. Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic GSK298772 Population comprised of participants in the safety population who received an active dose and for whom a GSK2982772 pharmacokinetic sample was obtained and analyzed. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose on Day 8 and Day 43

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	5 ^[57]	24 ^[58]
Units: Nanogram per milliliter
arithmetic mean (standard deviation)
Day 8;n=5,24	88.332 ± 96.5705	181.774 ± 322.8428
Day 43;n=5,23	33.994 ± 51.1033	142.792 ± 176.2630

Notes
[57] - Pharmacokinetic GSK298772 Population
[58] - Pharmacokinetic GSK298772 Population

No statistical analyses for this end point

Secondary: Post-dose plasma concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 hours

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End point title

Post-dose plasma concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 hours ^[59]

End point description

Blood samples were collected on Day 1, Day 8 and Day 43 for determining post-dose plasma concentrations of GSK2982772. Pharmacokinetic parameters were determined using standard non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Days 1, 8 and 43: 1, 2, 4 and 6 hours post-dose

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	5 ^[60]	27 ^[61]
Units: Nanogram per milliliter
arithmetic mean (standard deviation)
Day 1;1 hour;n=5,27	851.000 ± 375.5110	953.037 ± 556.4630
Day 1;2 hour;n=5,27	656.000 ± 386.5741	911.630 ± 376.7128
Day 1;4 hour;n=5,27	269.600 ± 156.3052	421.215 ± 211.7969
Day 1;6 hour;n=5,27	120.240 ± 54.6881	382.419 ± 485.6076
Day 8;1 hour;n=5,23	796.600 ± 397.7120	881.783 ± 550.4666
Day 8;2 hour;n=5,24	689.000 ± 317.5602	930.958 ± 446.0379
Day 8;4 hour;n=5,24	265.000 ± 129.6360	520.958 ± 324.4127
Day 8;6 hour;n=5,23	112.280 ± 78.0491	444.470 ± 358.1685
Day 43;1 hour;n=5,23	672.200 ± 165.4470	862.487 ± 501.4882
Day 43;2 hour;n=5,23	598.600 ± 253.0036	872.652 ± 354.1155
Day 43;4 hour;n=5,23	313.200 ± 226.0845	553.783 ± 430.5811
Day 43;6 hour;n=5,23	177.980 ± 192.6731	332.522 ± 240.9716

Notes
[60] - Pharmacokinetic GSK298772 Population
[61] - Pharmacokinetic GSK298772 Population

No statistical analyses for this end point

Secondary: Trough plasma concentration of GSK2982772 on Day 85

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End point title

Trough plasma concentration of GSK2982772 on Day 85 ^[62]

End point description

Blood samples were collected to evaluate plasma concentration of GSK2982772. Pharmacokinetic parameters including trough plasma concentration was determined using standard non-compartmental methods. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Day 85

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	5 ^[63]	17 ^[64]
Units: Nanogram per milliliter
arithmetic mean (standard deviation)	54.64 ± 50.714	391.11 ± 694.270

Notes
[63] - Pharmacokinetic GSK298772 Population
[64] - Pharmacokinetic GSK298772 Population

No statistical analyses for this end point

Secondary: Pre-dose plasma concentrations of methotrexate on Days 1, 8 and 43

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End point title

Pre-dose plasma concentrations of methotrexate on Days 1, 8 and 43

End point description

Blood samples were collected on Day 1, Day 8 and Day 43 for determining pre-dose plasma concentrations of methotrexate. Pharmacokinetic parameters were determined using standard non-compartmental methods. Only participants who received methotrexate during the study were included. Pharmacokinetic Methotrexate Population comprised of participants in the safety population who received an active dose and for whom a Methotrexate pharmacokinetic sample was obtained and analyzed. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Pre-dose on Days 1, 8 and 43

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[65]	13 ^[66]	5 ^[67]	22 ^[68]
Units: Nanogram per milliliter
arithmetic mean (standard deviation)
Day 1;n=3,13,5,22	0.450 ± 0.7794	16.236 ± 56.4280	0.546 ± 0.7909	6.309 ± 15.4993
Day 8;n=3,12,5,17	1.117 ± 1.9341	0.509 ± 0.9879	4.640 ± 10.3754	11.939 ± 47.4493
Day 43;n=3,11,5,19	36.000 ± 62.3538	0.909 ± 2.0658	1.512 ± 3.3809	1.445 ± 3.1606

Notes
[65] - Pharmacokinetic Methotrexate Population
[66] - Pharmacokinetic Methotrexate Population
[67] - Pharmacokinetic Methotrexate Population
[68] - Pharmacokinetic Methotrexate Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in C-Reactive Protein (CRP)

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End point title

Percent change from Baseline in C-Reactive Protein (CRP)

End point description

CRP is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of CRP. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[69]	14 ^[70]	5 ^[71]	24 ^[72]
Units: Percent change
arithmetic mean (standard deviation)
Day 43;n=3,14,5,24	-24.02 ± 53.259	63.02 ± 331.286	-10.37 ± 94.318	12.68 ± 107.207
Day 85;n=3,14,5,22	-43.62 ± 49.968	220.05 ± 828.334	-16.42 ± 70.096	274.25 ± 879.900

Notes
[69] - Safety Population
[70] - Safety Population
[71] - Safety Population
[72] - Safety Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in Interleukin 6 (IL6)

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End point title

Percent change from Baseline in Interleukin 6 (IL6)

End point description

IL6 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of IL6. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[73]	14 ^[74]	5 ^[75]	24 ^[76]
Units: Percent change
arithmetic mean (standard deviation)
Day 43;n=3,14,5,24	89.12 ± 96.649	55.00 ± 257.661	-3.95 ± 66.008	74.49 ± 358.187
Day 85;n=3,14,5,22	5.21 ± 16.978	27.52 ± 97.215	-24.44 ± 67.817	0.52 ± 106.029

Notes
[73] - Safety Population
[74] - Safety Population
[75] - Safety Population
[76] - Safety Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in Matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-13

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End point title

Percent change from Baseline in Matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-13

End point description

MMP-1, MMP-3, and MMP-13 are an inflammatory biomarkers present in blood. Blood samples were collected at indicated time points for the assessment of MMP-1, MMP-3, and MMP-13. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[77]	14 ^[78]	5 ^[79]	24 ^[80]
Units: Percent change
arithmetic mean (standard deviation)
MMP-1;Day 43;n=3,14,5,24	-11.25 ± 6.591	-4.04 ± 23.016	-15.36 ± 13.399	-4.07 ± 27.244
MMP-1;Day 85;n=3,14,5,22	-19.77 ± 28.013	9.75 ± 41.645	-20.21 ± 19.417	-1.61 ± 28.420
MMP-3;Day 43;n=3,14,5,24	8.86 ± 27.501	6.07 ± 27.883	-26.82 ± 20.757	-4.07 ± 36.176
MMP-3;Day 85;n=3,14,5,22	32.61 ± 32.849	11.98 ± 42.337	-38.26 ± 19.306	-2.14 ± 34.751
MMP-13;Day 43;n=3,12,5,22	-6.45 ± 7.000	32.94 ± 139.157	-7.27 ± 34.373	-3.55 ± 29.506
MMP-13;Day 85;n=3,11,5,17	-34.65 ± 35.926	114.18 ± 223.386	-21.16 ± 31.372	67.91 ± 157.027

Notes
[77] - Safety Population
[78] - Safety Population
[79] - Safety Population
[80] - Safety Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in tissue inhibitor of metalloproteinases-1 (TIMP-1)

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End point title

Percent change from Baseline in tissue inhibitor of metalloproteinases-1 (TIMP-1)

End point description

TIMP-1 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of TIMP-1. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[81]	14 ^[82]	5 ^[83]	24 ^[84]
Units: Percent change
arithmetic mean (standard deviation)
Day 43;n=3,14,5,24	-1.82 ± 6.578	-9.89 ± 37.032	-7.39 ± 11.298	-5.59 ± 23.922
Day 85;n=3,14,5,22	35.61 ± 73.383	-2.63 ± 57.144	49.38 ± 114.161	-1.75 ± 33.789

Notes
[81] - Safety Population
[82] - Safety Population
[83] - Safety Population
[84] - Safety Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in monocyte chemo attractant protein-1 (MCP-1)

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End point title

Percent change from Baseline in monocyte chemo attractant protein-1 (MCP-1)

End point description

MCP-1 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of MCP-1. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[85]	14 ^[86]	5 ^[87]	23 ^[88]
Units: Percent change
arithmetic mean (standard deviation)
Day 43;n=3,14,5,23	-4.57 ± 19.262	388.23 ± 565.617	-4.37 ± 11.309	156.79 ± 297.549
Day 85;n=3,14,5,21	-33.39 ± 49.411	422.45 ± 514.842	-30.35 ± 36.118	199.94 ± 392.590

Notes
[85] - Safety Population
[86] - Safety Population
[87] - Safety Population
[88] - Safety Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in migration inhibitory factor (MIF)

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End point title

Percent change from Baseline in migration inhibitory factor (MIF)

End point description

MIF is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of MIF. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[89]	14 ^[90]	5 ^[91]	24 ^[92]
Units: Percent change
arithmetic mean (standard deviation)
Day 43;n=3,14,5,24	8.98 ± 29.041	4.69 ± 46.772	120.23 ± 362.931	34.46 ± 160.400
Day 85;n=3,14,5,22	15.39 ± 26.888	-15.72 ± 49.080	-11.80 ± 47.351	-5.76 ± 49.377

Notes
[89] - Safety Population
[90] - Safety Population
[91] - Safety Population
[92] - Safety Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in Myeloid-related Protein 8/14 (MRP8/14)

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End point title

Percent change from Baseline in Myeloid-related Protein 8/14 (MRP8/14)

End point description

MRP8/14 is an inflammatory biomarker present in blood. Blood samples were collected at indicated time points for the assessment of MRP8/14. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[93]	14 ^[94]	5 ^[95]	24 ^[96]
Units: Percent change
arithmetic mean (standard deviation)
Day 43;n=3,14,5,24	3.15 ± 47.472	25.14 ± 75.189	-49.21 ± 19.168	-22.95 ± 38.992
Day 85;n=3,14,5,22	13.84 ± 66.492	70.37 ± 199.467	-28.27 ± 17.112	-11.35 ± 77.927

Notes
[93] - Safety Population
[94] - Safety Population
[95] - Safety Population
[96] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone erosion total score by "Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS)" scoring system

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End point title

Change from Baseline in bone erosion total score by "Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS)" scoring system

End point description

A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone erosions. Individual location scores range from 0 (no erosions) to 10 (91 to 100 percent of bone eroded) based on the proportion of eroded bone compared to the “assessed bone volume” on all available images. The final bone erosion score was the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 250, with 0 implying no bone erosion and 250 implying 91 to 100 percent bone eroded. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[97]	13 ^[98]	5 ^[99]	24 ^[100]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=3,13,5,24	0.7 ± 1.15	0.6 ± 1.04	0.4 ± 1.52	-0.2 ± 1.83
Day 85;n=3,13,5,22	1.7 ± 2.89	1.3 ± 2.43	0.4 ± 1.52	-0.1 ± 2.21

Notes
[97] - Safety Population
[98] - Safety Population
[99] - Safety Population
[100] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone erosions by the Rheumatoid arthritis MRI quantitative (RAMRIQ) scoring system

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End point title

Change from Baseline in bone erosions by the Rheumatoid arthritis MRI quantitative (RAMRIQ) scoring system

End point description

RAMRIQ bone erosions (normalized) was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements of the volume of bone erosions divided by sum of the individual measurements of the bone volume. The total score ranged from 0 to 1, with 0 implying no erosive damage. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[101]	13 ^[102]	5 ^[103]	23 ^[104]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=2,13,5,23	-0.00160 ± 0.002550	-0.00110 ± 0.002265	-0.00072 ± 0.001662	-0.00069 ± 0.004145
Day 85;n=2,13,5,21	-0.00069 ± 0.001134	-0.00075 ± 0.001301	-0.00273 ± 0.003505	0.00059 ± 0.003946

Notes
[101] - Safety Population
[102] - Safety Population
[103] - Safety Population
[104] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone erosions by modified Cartilage Loss Scoring System (CARLOS)

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End point title

Change from Baseline in bone erosions by modified Cartilage Loss Scoring System (CARLOS)

End point description

Change from Baseline in bone erosions was planned to be assessed by modified CARLOS. Data was not collected for this outcome measure, as bone erosion is not a part of modified CARLOS and it was measured by OMERACT-RAMRIS scoring system in another outcome measure.

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[105]	0 ^[106]	0 ^[107]	0 ^[108]
Units: Scores on a scale
arithmetic mean (standard deviation)	±	±	±	±

Notes
[105] - Safety Population
[106] - Safety Population
[107] - Safety Population
[108] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in synovitis by OMERACT-RAMRIS scoring system

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End point title

Change from Baseline in synovitis by OMERACT-RAMRIS scoring system

End point description

A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[109]	13 ^[110]	5 ^[111]	24 ^[112]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=3,13,5,24	0.0 ± 1.73	0.3 ± 1.55	-0.4 ± 1.52	-0.3 ± 1.90
Day 85;n=3,13,5,22	0.3 ± 1.15	0.5 ± 2.67	-0.4 ± 1.52	-0.5 ± 2.20

Notes
[109] - Safety Population
[110] - Safety Population
[111] - Safety Population
[112] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in synovitis by RAMRIQ scoring system

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End point title

Change from Baseline in synovitis by RAMRIQ scoring system

End point description

RAMRIQ synovitis (normalised) was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements of the volume of enhancing pannus (VEP) divided by sum of the individual measurements of the joint volume. The total score ranged from 0 to 1, with 0 implying no synovitis. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[113]	13 ^[114]	5 ^[115]	23 ^[116]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=2,13,5,23	-0.0570 ± 0.02302	-0.0165 ± 0.04302	-0.0592 ± 0.06931	-0.0084 ± 0.10490
Day 85;n=2,13,5,21	-0.0659 ± 0.01625	0.0251 ± 0.12286	-0.0270 ± 0.07061	-0.0107 ± 0.11472

Notes
[113] - Safety Population
[114] - Safety Population
[115] - Safety Population
[116] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in synovitis by modified CARLOS

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End point title

Change from Baseline in synovitis by modified CARLOS

End point description

Change from Baseline in synovitis was planned to be assessed by modified CARLOS. Data was not collected for this outcome measure, as synovitis is not a part of modified CARLOS and it was measured by OMERACT-RAMRIS scoring system in another outcome measure.

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[117]	0 ^[118]	0 ^[119]	0 ^[120]
Units: Scores on a scale
arithmetic mean (standard deviation)	±	±	±	±

Notes
[117] - Safety Population
[118] - Safety Population
[119] - Safety Population
[120] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone edema by OMERACT-RAMRIS scoring system

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End point title

Change from Baseline in bone edema by OMERACT-RAMRIS scoring system

End point description

A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[121]	13 ^[122]	5 ^[123]	24 ^[124]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=3,13,5,24	-1.0 ± 1.73	-0.2 ± 1.52	-0.8 ± 3.27	-0.9 ± 2.47
Day 85;n=3,13,5,22	0.3 ± 0.58	0.3 ± 1.38	-4.4 ± 6.80	-1.1 ± 2.59

Notes
[121] - Safety Population
[122] - Safety Population
[123] - Safety Population
[124] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone edema by RAMRIQ scoring system

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End point title

Change from Baseline in bone edema by RAMRIQ scoring system

End point description

RAMRIQ bone edema (normalised) was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements of the Volume of bone edema divided by sum of the individual measurements of the bone volume.. The total score ranged from 0 to 1, with 0 implying no bone marrow lesions. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[125]	13 ^[126]	5 ^[127]	22 ^[128]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=2,13,5,22	-0.00396 ± 0.000647	-0.00463 ± 0.007465	-0.01963 ± 0.031481	-0.00095 ± 0.018745
Day 85;n=2,13,5,21	0.00116 ± 0.010166	-0.00229 ± 0.010143	-0.03921 ± 0.055431	-0.00384 ± 0.016126

Notes
[125] - Safety Population
[126] - Safety Population
[127] - Safety Population
[128] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone edema by modified CARLOS

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End point title

Change from Baseline in bone edema by modified CARLOS

End point description

Change from Baseline in bone edema was planned to be assessed by modified CARLOS. Data was not collected for this outcome measure, as bone edema is not a part of modified CARLOS and it was measured by OMERACT-RAMRIS scoring system in another outcome measure.

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[129]	0 ^[130]	0 ^[131]	0 ^[132]
Units: Scores on a scale
arithmetic mean (standard deviation)	±	±	±	±

Notes
[129] - Safety Population
[130] - Safety Population
[131] - Safety Population
[132] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in joint space narrowing by OMERACT-RAMRIS scoring system

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End point title

Change from Baseline in joint space narrowing by OMERACT-RAMRIS scoring system

End point description

Change from Baseline in joint space narrowing was planned to be assessed by OMERACT-RAMRIS scoring system. Data was not collected for this outcome measure, as joint space narrowing is not a part of OMERACT-RAMRIS scoring system and it was measured by modified CARLOS in another outcome.

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[133]	0 ^[134]	0 ^[135]	0 ^[136]
Units: Scores on a scale
arithmetic mean (standard deviation)	±	±	±	±

Notes
[133] - Safety Population
[134] - Safety Population
[135] - Safety Population
[136] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in joint space narrowing by RAMRIQ scoring system

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End point title

Change from Baseline in joint space narrowing by RAMRIQ scoring system

End point description

RAMRIQ joint space narrowing was a quantitative measurement from the bones and synovial capsules of the joints from the most affected (or dominant hand if equally affected). It was calculated as the sum of the individual measurements (in millimeter) for the joints measured. The minimum possible total score is 0 implying complete loss of the joint space. The maximum possible total score will be largest possible joint space. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[137]	13 ^[138]	5 ^[139]	23 ^[140]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=2,13,5,23	1.121 ± 1.4793	0.378 ± 1.3394	0.484 ± 2.8980	-0.335 ± 1.4365
Day 85;n=2,13,5,21	0.534 ± 0.8910	0.216 ± 0.6974	0.235 ± 2.2525	-0.433 ± 1.1205

Notes
[137] - Safety Population
[138] - Safety Population
[139] - Safety Population
[140] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in joint space narrowing by modified CARLOS

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End point title

Change from Baseline in joint space narrowing by modified CARLOS

End point description

A total of 20 locations in the hand and wrist were evaluated for CARLOS joint space narrowing/cartilage loss. Individual location scores range from 0 (no cartilage loss or Joint Space Narrowing) to 4 (complete ankylosis) in increments of 0.5 based on the amount of narrowing present in a given joint. The final cartilage loss score was the sum of the individual location scores. The total score from 20 location ranged from 0 to 80, with 0 implying no cartilage loss at any location and 80 implying complete ankylosis. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[141]	13 ^[142]	5 ^[143]	24 ^[144]
Units: Scores on a scale
arithmetic mean (standard deviation)
Day 43;n=3,13,5,24	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.08 ± 0.408
Day 85;n=3,13,5,22	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.09 ± 0.426

Notes
[141] - Safety Population
[142] - Safety Population
[143] - Safety Population
[144] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in exchange rate (Ktrans)

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End point title

Change from Baseline in exchange rate (Ktrans)

End point description

Contrast agent volume transfer constant (Ktrans) relates to the exchange of contrast agent between the blood plasma and the tissue extravascular extracellular spaces and reflects blood flow and capillary permeability. Ktrans was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) tracer kinetic modeling in the most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[145]	9 ^[146]	5 ^[147]	19 ^[148]
Units: Per minute
arithmetic mean (standard deviation)
Day 43;n=2,9,5,19	0.0012 ± 0.00076	0.0022 ± 0.01214	-0.0095 ± 0.01716	-0.0018 ± 0.01443
Day 85;n=2,9,5,17	0.0002 ± 0.01726	-0.0021 ± 0.01385	-0.0073 ± 0.00618	-0.0043 ± 0.01747

Notes
[145] - Safety Population
[146] - Safety Population
[147] - Safety Population
[148] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in interstitial volume (Ve)

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End point title

Change from Baseline in interstitial volume (Ve)

End point description

Interstitial volume (Ve) is the fractional volume of the extravascular extracellular (EC) space per unit volume tissue within which contrast agent can accumulate. Ve was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[149]	9 ^[150]	5 ^[151]	18 ^[152]
Units: Ratio of EC space to tissue volume
arithmetic mean (standard deviation)
Day 43;n=2,9,5,18	-0.305 ± 0.3128	-0.066 ± 0.3615	-0.140 ± 0.4825	0.073 ± 0.4044
Day 85;n=2,9,5,15	0.009 ± 0.7840	-0.024 ± 0.2450	-0.278 ± 0.5170	0.113 ± 0.4664

Notes
[149] - Safety Population
[150] - Safety Population
[151] - Safety Population
[152] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in fractional volume of blood plasma (Vp)

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End point title

Change from Baseline in fractional volume of blood plasma (Vp)

End point description

Fractional volume of blood plasma (Vp) is the fractional volume of blood plasma per unit volume of tissue. Vp was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[153]	9 ^[154]	5 ^[155]	19 ^[156]
Units: Ratio of plasma volume to tissue volume
arithmetic mean (standard deviation)
Day 43;n=2,9,5,19	0.0018 ± 0.00166	0.0007 ± 0.00678	-0.0023 ± 0.00786	-0.0007 ± 0.00358
Day 85;n=2,9,5,17	0.0000 ± 0.00019	-0.0022 ± 0.00407	-0.0001 ± 0.00272	-0.0007 ± 0.00282

Notes
[153] - Safety Population
[154] - Safety Population
[155] - Safety Population
[156] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in initial rate of enhancement (IRE)

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End point title

Change from Baseline in initial rate of enhancement (IRE)

End point description

Initial Rate of Enhancement (IRE) is a measure of how quickly tissue enhances over 60 seconds following administration of contrast agent. IRE was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[157]	9 ^[158]	5 ^[159]	19 ^[160]
Units: Millimole per second
arithmetic mean (standard deviation)
Day 43;n=2,9,5,19	-0.00002 ± 0.000044	0.00008 ± 0.000538	-0.00043 ± 0.000750	-0.00008 ± 0.000575
Day 85;n=2,9,5,17	-0.00011 ± 0.000566	-0.00010 ± 0.000542	-0.00037 ± 0.000271	-0.00014 ± 0.000735

Notes
[157] - Safety Population
[158] - Safety Population
[159] - Safety Population
[160] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in maximal signal intensity enhancement (ME)

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End point title

Change from Baseline in maximal signal intensity enhancement (ME)

End point description

Maximum enhancement (ME) is a measure of the maximum concentration of contrast agent in the tissue over the duration of the DCE-MRI time series. ME was measured by DCE-MRI in most affected hand/wrist at indicated time points. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	2 ^[161]	9 ^[162]	5 ^[163]	19 ^[164]
Units: Millimole
arithmetic mean (standard deviation)
Day 43;n=2,9,5,19	-0.0300 ± 0.00994	0.0029 ± 0.05405	-0.0531 ± 0.06876	0.0007 ± 0.06159
Day 85;n=2,9,5,17	-0.0533 ± 0.00473	-0.0138 ± 0.05168	-0.0584 ± 0.06009	-0.0074 ± 0.07180

Notes
[161] - Safety Population
[162] - Safety Population
[163] - Safety Population
[164] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) scores

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End point title

Change from Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) scores

End point description

The DAS28-CRP is a composite measure of inflammation in rheumatoid arthritis calculated from the sum of tender joint count 28 (TJC28), swollen joint count (SJC28), CRP and patient global assessment of disease activity (PtGA). The formula used to calculate DAS28 score was 0.56 multiplied by square root of TJC28 plus 0.28 multiplied by square root of SJC28 plus 0.36 log of (CRP plus 1) plus 0.014 multiplied by PtGA plus 0.96. Scores of DAS28-CRP ranged from 0.96 to 9.4 with higher scores indicating greater disease burden. A DAS28-CRP score of <=2.6 suggested remission, <3.2 suggested a low level of disease activity, while a score of >5.1 suggested a high level of disease activity. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1 pre-dose) and Day 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[165]	12 ^[166]	5 ^[167]	22 ^[168]
Units: Scores on a scale
least squares mean (confidence interval 95%)	-1.00 (-2.45 to 0.46)	-0.87 (-1.57 to -0.17)	-1.47 (-2.60 to 0.35)	-1.23 (-1.75 to 0.71)

Notes
[165] - Safety Population
[166] - Safety Population
[167] - Safety Population
[168] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants achieving categorical DAS28-CRP response using European League Against Rheumatism [EULAR] response

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End point title

Number of participants achieving categorical DAS28-CRP response using European League Against Rheumatism [EULAR] response

End point description

DAS28-CRP scores were categorized using EULAR response criteria. Response at a given time point was defined based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to Baseline. The definition of no response, moderate response and good response was as; if current DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2: good response), (>0.6 to <=1.2: moderate response) and (<=0.6: no response); if current DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline value (>1.2: moderate response), (>0.6 to <=1.2: moderate response) and (<=0.6: no response) and if current DAS28 >5.1 and DAS28 decrease from Baseline value (>1.2: moderate response), (>0.6 to <=1.2: no response) and (<=0.6: no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Day 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[169]	12 ^[170]	5 ^[171]	22 ^[172]
Units: Participants
No response	2	6	1	7
Moderate response	0	4	2	8
Good response	1	2	2	7

Notes
[169] - Safety Population
[170] - Safety Population
[171] - Safety Population
[172] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants achieving categorical American college of rhumatology20/50/70 (ACR20/50/70) response

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End point title

Number of participants achieving categorical American college of rhumatology20/50/70 (ACR20/50/70) response

End point description

The ACR score was based on improvement from Baseline in tender joint counts and swollen joint counts. A participant had achieved ACR20 if he experienced >=20 percent improvement from Baseline in Tender Joint count 28 (TJC28) and Swollen Joint Count 28 (SJC28) and a >=20 percent improvement from Baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, C-reactive protein and Health Assessment Questionnaire – Disability Index (HAQ-DI). Similarly, ACR50 and ACR70 are calculated using 50 or 70 percent improvement from baseline respectively. For all visits, if any of the component scores were missing; then those scores were considered as not having met the criteria for improvement.

End point type

Secondary

End point timeframe

Day 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	3 ^[173]	15 ^[174]	5 ^[175]	28 ^[176]
Units: Participants
ACR20	1	6	3	12
ACR50	1	2	0	5
ACR70	1	1	0	4

Notes
[173] - Safety Population
[174] - Safety Population
[175] - Safety Population
[176] - Safety Population

No statistical analyses for this end point

Other pre-specified: Change from Baseline in joint volume

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End point title

Change from Baseline in joint volume

End point description

Joint volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

End point type

Other pre-specified

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[177]	0 ^[178]	0 ^[179]	0 ^[180]
Units: Cubic millimeter
arithmetic mean (standard deviation)	±	±	±	±

Notes
[177] - Safety Population
[178] - Safety Population
[179] - Safety Population
[180] - Safety Population

No statistical analyses for this end point

Other pre-specified: Change from Baseline in enhancing volume

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End point title

Change from Baseline in enhancing volume

End point description

Enhancing volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

End point type

Other pre-specified

End point timeframe

Baseline (Day 1 pre-dose), Days 43 and 85

End point values	Placebo BID	Placebo TID	GSK2982772 60 mg BID	GSK2982772 60 mg TID
Number of subjects analysed	0 ^[181]	0 ^[182]	0 ^[183]	0 ^[184]
Units: Cubic millimeter
arithmetic mean (standard deviation)	±	±	±	±

Notes
[181] - Safety Population
[182] - Safety Population
[183] - Safety Population
[184] - Safety Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On-therapy non-SAEs and SAEs were reported from start of study treatment and up to 112 days

Adverse event reporting additional description

Non-SAE and SAEs were reported for Safety Population. Adverse events were presented treatment-wise.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Placebo BID

Reporting group description

Participants received placebo orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Reporting group title

Placebo TID

Reporting group description

Reporting group title

GSK2982772 60mg BID

Reporting group description

Participants received GSK2982772 orally twice daily (BID) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Reporting group title

GSK2982772 60mg TID

Reporting group description

three times daily (TID) (approximately 8 hours apart) for 84 days (12 weeks). Participants received methotrexate for the treatment of RA during conduct of the study, if required.

Serious adverse events	Placebo BID	Placebo TID	GSK2982772 60mg BID	GSK2982772 60mg TID
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 28 (7.14%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Tibia fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo BID	Placebo TID	GSK2982772 60mg BID	GSK2982772 60mg TID
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	10 / 15 (66.67%)	3 / 5 (60.00%)	16 / 28 (57.14%)
General disorders and administration site conditions
Peripheral swelling
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	2	0	0
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	1	0	1
Influenza like illness
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	0	0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Investigations
Blood pressure increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 28 (7.14%)
occurrences all number	0	1	0	2
Transaminases increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	1 / 28 (3.57%)
occurrences all number	0	0	2	1
Cardiac disorders
Bundle branch block left
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Palpitations
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Ventricular arrhythmia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 28 (0.00%)
occurrences all number	0	0	2	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	2	0	1
Dizziness
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 28 (7.14%)
occurrences all number	0	0	0	3
Sciatica
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Somnolence
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Vascular headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 28 (0.00%)
occurrences all number	0	0	1	0
Eye disorders
Vision blurred
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Visual impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Diarrhoea
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 28 (0.00%)
occurrences all number	0	0	1	0
Skin and subcutaneous tissue disorders
Alopecia areata
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Dermatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Macule
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	2
Pruritus
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 28 (7.14%)
occurrences all number	1	1	0	2
Synovial cyst
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	1 / 28 (3.57%)
occurrences all number	0	0	1	1
Back pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Joint swelling
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Pain in extremity
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	1	0	1
Pharyngitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	1	0	1
Bronchitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Genital herpes
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Oral herpes
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	2
Pertussis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Respiratory tract infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	0	0
Respiratory tract infection viral
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Skin infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Upper respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0
Viral infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Viral upper respiratory tract infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	0	0
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	1
Hypercholesterolaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 28 (0.00%)
occurrences all number	0	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

25 May 2016

Protocol Amendment 01 incorporates the addition of risk text for drug interaction with Pglycoprotein (Pgp) inhibitors and narrow therapeutic index (NTI) CYP3A4 substrates, an updated list of prohibited medications plus some minor protocol clarifications and administrative changes.

14 Jul 2016

Protocol Amendment 02 incorporates addition of suicidal ideation and behaviour (SIB) withdrawal criteria plus other minor protocol clarifications and administrative changes.

20 Apr 2017

Protocol Amendment 03 incorporates change in dosing regimen from 60 mg BID to 60 mg TID, restrictions on Janus Kinase (JAK) inhibitors, defined non-reproductive potential criteria in Exclusion 11, change to clinical laboratory criteria in Exclusion 23, addition of evaluation of joint space narrowing with MRI, flexibility in scheduling with MRI and synovial biopsy, some minor protocol clarifications and administrative changes.

03 Aug 2017

A country specific amendment for Germany (only applicable in Germany) which reinstates the clinical laboratory criteria in Exclusion 23 and Haematologic Stopping Criteria in Section 5.4.5 that was changed in Amendment 03.

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 multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with moderate to severe rheumatoid arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with non-serious adverse events (nSAEs) and serious adverse events (SAEs) as a measure of safety and tolerability

Primary: Number of participants with non-serious adverse events (nSAEs) and serious adverse events (SAEs) as a measure of safety and tolerability

Primary: Number of participants with worst case clinical chemistry parameters of potential clinical importance (PCI)

Primary: Number of participants with worst case clinical chemistry parameters of potential clinical importance (PCI)

Primary: Number of participants with worst case hematology parameters of PCI

Primary: Number of participants with worst case hematology parameters of PCI

Primary: Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by dipstick method

Primary: Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by dipstick method

Primary: Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by microscopy method

Primary: Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline by microscopy method

Primary: Change from Baseline in electrocardiogram (ECG) heart rate at indicated time points

Primary: Change from Baseline in electrocardiogram (ECG) heart rate at indicated time points

Primary: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time points

Primary: Change from Baseline in ECG PR interval, QRS duration, QT interval, QTcB and QTcF at indicated time points

Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time points

Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at indicated time points

Primary: Change from Baseline in respiratory rate at indicated time points

Primary: Change from Baseline in respiratory rate at indicated time points

Primary: Change from Baseline in body temperature at indicated time points

Primary: Change from Baseline in body temperature at indicated time points

Primary: Change from Baseline in vital sign-heart rate at indicated time points

Primary: Change from Baseline in vital sign-heart rate at indicated time points

Secondary: Pre-dose plasma concentrations of GSK2982772 on Days 8 and 43

Secondary: Pre-dose plasma concentrations of GSK2982772 on Days 8 and 43

Secondary: Post-dose plasma concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 hours

Secondary: Post-dose plasma concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 hours

Secondary: Trough plasma concentration of GSK2982772 on Day 85

Secondary: Trough plasma concentration of GSK2982772 on Day 85

Secondary: Pre-dose plasma concentrations of methotrexate on Days 1, 8 and 43

Secondary: Pre-dose plasma concentrations of methotrexate on Days 1, 8 and 43

Secondary: Percent change from Baseline in C-Reactive Protein (CRP)

Secondary: Percent change from Baseline in C-Reactive Protein (CRP)

Secondary: Percent change from Baseline in Interleukin 6 (IL6)

Secondary: Percent change from Baseline in Interleukin 6 (IL6)

Secondary: Percent change from Baseline in Matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-13

Secondary: Percent change from Baseline in Matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-13

Secondary: Percent change from Baseline in tissue inhibitor of metalloproteinases-1 (TIMP-1)

Secondary: Percent change from Baseline in tissue inhibitor of metalloproteinases-1 (TIMP-1)

Secondary: Percent change from Baseline in monocyte chemo attractant protein-1 (MCP-1)

Secondary: Percent change from Baseline in monocyte chemo attractant protein-1 (MCP-1)

Secondary: Percent change from Baseline in migration inhibitory factor (MIF)

Secondary: Percent change from Baseline in migration inhibitory factor (MIF)

Secondary: Percent change from Baseline in Myeloid-related Protein 8/14 (MRP8/14)

Secondary: Percent change from Baseline in Myeloid-related Protein 8/14 (MRP8/14)

Secondary: Change from Baseline in bone erosion total score by "Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS)" scoring system

Secondary: Change from Baseline in bone erosion total score by "Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS)" scoring system

Secondary: Change from Baseline in bone erosions by the Rheumatoid arthritis MRI quantitative (RAMRIQ) scoring system

Secondary: Change from Baseline in bone erosions by the Rheumatoid arthritis MRI quantitative (RAMRIQ) scoring system

Secondary: Change from Baseline in bone erosions by modified Cartilage Loss Scoring System (CARLOS)

Secondary: Change from Baseline in bone erosions by modified Cartilage Loss Scoring System (CARLOS)

Secondary: Change from Baseline in synovitis by OMERACT-RAMRIS scoring system

Secondary: Change from Baseline in synovitis by OMERACT-RAMRIS scoring system

Secondary: Change from Baseline in synovitis by RAMRIQ scoring system

Secondary: Change from Baseline in synovitis by RAMRIQ scoring system

Secondary: Change from Baseline in synovitis by modified CARLOS

Secondary: Change from Baseline in synovitis by modified CARLOS

Secondary: Change from Baseline in bone edema by OMERACT-RAMRIS scoring system

Secondary: Change from Baseline in bone edema by OMERACT-RAMRIS scoring system

Secondary: Change from Baseline in bone edema by RAMRIQ scoring system

Secondary: Change from Baseline in bone edema by RAMRIQ scoring system

Secondary: Change from Baseline in bone edema by modified CARLOS

Secondary: Change from Baseline in bone edema by modified CARLOS

Secondary: Change from Baseline in joint space narrowing by OMERACT-RAMRIS scoring system

Secondary: Change from Baseline in joint space narrowing by OMERACT-RAMRIS scoring system

Secondary: Change from Baseline in joint space narrowing by RAMRIQ scoring system

Secondary: Change from Baseline in joint space narrowing by RAMRIQ scoring system

Secondary: Change from Baseline in joint space narrowing by modified CARLOS

Secondary: Change from Baseline in joint space narrowing by modified CARLOS

Secondary: Change from Baseline in exchange rate (Ktrans)

Secondary: Change from Baseline in exchange rate (Ktrans)

Clinical Trial Results:
A multicentre, randomised, double-blind (sponsor-unblinded), placebo-controlled study to investigate the safety and tolerability, pharmacokinetics, pharmacodynamics, and efficacy of GSK2982772 in subjects with moderate to severe rheumatoid arthritis