Arthritis, Rheumatoid
Conditions
Keywords
efficacy, safety, pharmacokinetics, pharmacodynamics, Rheumatoid Arthritis, autoimmune
Brief summary
This study is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with moderate to severe RA who are currently being treated with disease modifying anti-rheumatic drugs (DMARDs). The primary objective of the study is to investigate the safety and tolerability of repeat oral doses of GSK2982772 in subjects with moderate to severe RA. In addition to the PK, a number of experimental and clinical endpoints will be employed to obtain information on the PD, and preliminary efficacy in subjects with active RA. Although no formal hypothesis will be tested, these endpoints will enable a broader understanding of the mechanism of action and potential for clinical efficacy of GSK2982772 in RA. After a screening period of up to 30 days, approximately 24 subjects will be randomized to receive either GSK2982772 or placebo for 84 days (12 weeks), followed by a follow-up period (28 days). The total duration of participation in the study will be approximately 20 weeks from screening to the last study visit.
Interventions
DRUGGSK2982772 60 mg
GSK2982772 is available as a 30 mg white to almost white, round film coated tablet which will be administered as two tablets thrice daily as directed.
DRUGPlacebo
Placebo is available as a white to almost white, round film coated tablet which will be administered as two tablets thrice daily as directed.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 75 years of age inclusive, at the time of signing the informed consent. * Subjects that do not have any medical conditions, other than moderate to severe RA, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with study assessments or integrity of the data. These medical conditions should be stable at the time of screening and are expected to remain stable for the duration of the study. * Subject has had a confirmed diagnosis of rheumatoid arthritis according to the revised 2010 ACR-EULAR classification criteria. * Disease duration of \>=12 weeks (time from onset of patient-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists) at screening. * Swollen joint count of \>=4 (28-joint count) and tender joint count \>=4 (28-joint count) at screening. * Subject has a DAS28 CRP disease activity score of \>= 3.2 and CRP \>= 5.0 mg/liter (L) (\>=4.76 nanomole (nmol)/L) at screening. * Subject must have received at least 12 weeks of non-biologic DMARD monotherapy or MTX/DMARD combination therapy prior to screening and must be on stable dose throughout the study. * Subject is naive to any biological therapies for RA or subject may have had previous exposure to a single anti-tumor necrosis factor (TNF) biologic agent which was discontinued for reasons other than primary non-response more than 8 weeks (or 5 half lives whichever is longer) from first dose. * For subjects who have consented to synovial joint biopsy: • Subject has an involved knee, wrist, or ankle suitable for biopsy, as assessed by a rheumatologist at screening. * A body mass index (BMI) within range of 18.5 - 35 kilogram/meter\^2 (Kg/m\^2) (inclusive) at screening. * Male and female subjects Males: Male subjects with female partners of child bearing potential must comply with the contraception requirements specified in the protocol. Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[HCG\] test), not lactating, and at least one of the following conditions applies: * Non-reproductive potential as defined as pre-menopausal females with either documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy. For Postmenopausal females as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.. * Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until at least 30 days after the last dose of study medication and completion of the follow-up visit. * The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. * Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Exclusion criteria
* Subject with a positive anti-double stranded deoxyribonucleic acid (DNA \[anti-dsDNA\]) and confirmed diagnosis of systemic lupus erythematosus (SLE). * Subject with current history of Suicidal Ideation Behavior (SIB) as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide. * An active infection, or a history of infections as follows: * Hospitalization for treatment of infection within 60 days before first dose (Day 1). * Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria). * Use of parenteral (intravenous \[IV\] or intramuscular) antibiotics (antibacterials, antivirals, antifungals, or antiparasitic agents) for an infection within 60 days before first dose. * A history of opportunistic infections within 1 year of screening (e.g. pneumocystis jirovecii, cytomegalovirus \[CMV\] pneumonitis, aspergillosis). This does not include infections that may occur in immunocompetent individuals, such as fungal nail infections or vaginal candidiasis, unless it is of an unusual severity or recurrent nature. * Recurrent or chronic infection or other active infection that, in the opinion of the Investigator might cause this study to be detrimental to the patient. * History of Tuberculosis (TB), irrespective of treatment status. * A positive diagnostic TB test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative. In cases where the QuantiFERON or T-spot test is positive, but a locally-read follow up chest x-ray, shows no evidence of current or previous pulmonary tuberculosis, the subject may be eligible for the study at the discretion of the Investigator and GSK Medical Monitor. * Electrocardiogram QT interval corrected for heart rate (QTc) \> 450 milliseconds (msec) or QTc \> 480 msec for subjects with bundle branch block at screening. The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual over read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined and documented prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used. * Alanine aminotransferase (ALT) \>2x upper limit of normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent) at screening. * Current active or chronic history of liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Current or history of renal disease or estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation \<60 milliliter (mL)/minute (min)/1.73 m\^2 at screening. * Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency. * A major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. * Any planned surgical procedures including surgical joint procedures (e.g., intra-articular, tendon sheath, or bursal corticosteroid injections) during the study. * A history of malignant neoplasm within the last 5 years, except for adequately treated non-metastatic cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix that has been fully treated and shows no evidence of recurrence. * Has undergone surgery including synovectomy or arthroplasty on the joint chosen for biopsy and/or magnetic resonance imaging (MRI). * The subject has a history of any other joint disease other than RA at the knee, wrist or ankle joint chosen for biopsy and/or MRI (e.g., gout, pseudogout, osteoarthritis). * Has undergone intra-articular corticosteroid injection, arthrocentesis or synovial biopsy on any joint within 6 weeks of screening. * A known allergy to lidocaine or other local anesthetics (only applies to subjects who consent for synovial biopsy procedures). * Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but are not limited to: * Intracranial aneurysm clips (except SugitaTM) or other metallic objects, * History of intra-orbital metal fragments that have not been removed by a medical professional. * Pacemakers or other implanted cardiac rhythm management devices and non-MR compatible heart valves, * Inner ear implants, * History of claustrophobia which may impact participation. * The subject has received treatment with the prohibited therapies listed in the protocol, or changes to those treatments, within the prescribed timeframe. • Other medications (including vitamins, herbal and dietary supplements) will be considered on a case-by-case basis, and will be allowed if in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety. * History of alcohol or drug abuse that would interfere with the ability to comply with the study. * History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation. * Received a live or attenuated vaccine within 30 days of randomization or plan to receive a vaccination during the study until half-lives (or 2 days) plus 30 days after receiving GSK2982772. * Contraindication to gadolinium contrast agent in accordance with local guidelines. * The subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer before the first dose of study medication, or plans to take part in another clinical trial at the same time as participating in this clinical trial. * Hemoglobin \<9 grams/deciliter (g/dL);hematocrit \<30 percent, white blood cell count =\<3,000/millimeter\^3 (mm\^3) (=\<3.0 x 10\^9/L); platelet count =\<100,000/ microliter (μL) (=\<100 x 10\^9/L); absolute neutrophil count =\<1.5 x 10\^9/L at screening. For subjects recruited in Germany: hemoglobin \<11 g/dL at screening. * Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should be excluded. * A positive serology for human immunodeficiency virus (HIV) 1 or 2 at screening. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months. * Exposure to more than 4 investigational medicinal products within 12 months prior to the first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Temperature at Indicated Time Points | Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85 | 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. |
| Change From Baseline in Vital Sign-heart Rate at Indicated Time Points | Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85 | Vital sign-heart rate was planned to be assessed as a measure of safety and tolerability. |
| Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Up to Day 112 | 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. |
| Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Up to Day 112 | 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. |
| Number of Participants With Worst Case Hematology Parameters of PCI | Up to Day 112 | 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. |
| Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Up to Day 112 | 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. |
| Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | Up to Day 112 | 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. |
| Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85 | 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. |
| Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85 | 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. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85 | 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. |
| Change From Baseline in Respiratory Rate at Indicated Time Points | Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
| Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Bone Erosions by Modified Cartilage Loss Scoring System (CARLOS) | Baseline (Day 1 pre-dose), Days 43 and 85 | Change from Baseline in bone erosions was planned to be assessed by modified CARLOS. |
| Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Synovitis by RAMRIQ Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Synovitis by Modified CARLOS | Baseline (Day 1 pre-dose), Days 43 and 85 | Change from Baseline in synovitis was planned to be assessed by modified CARLOS. |
| Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Bone Edema by RAMRIQ Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Bone Edema by Modified CARLOS | Baseline (Day 1 pre-dose), Days 43 and 85 | Change from Baseline in bone edema was planned to be assessed by modified CARLOS. |
| Change From Baseline in Joint Space Narrowing by OMERACT-RAMRIS Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | Change from Baseline in joint space narrowing was planned to be assessed by OMERACT-RAMRIS scoring system. |
| Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Joint Space Narrowing by Modified CARLOS | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Exchange Rate (Ktrans) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Interstitial Volume (Ve) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Initial Rate of Enhancement (IRE) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) Scores | Baseline (Day 1 pre-dose) and Day 85 | 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. |
| Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Day 85 | 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. |
| Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | Day 85 | 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. |
| Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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. |
| Pre-dose Plasma Concentrations of GSK2982772 on Days 8 and 43 | Pre-dose on Day 8 and Day 43 | 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. |
| Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Days 1, 8 and 43: 1, 2, 4 and 6 hours post-dose | 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. |
| Trough Plasma Concentration of GSK2982772 on Day 85 | Day 85 | Blood samples were collected to evaluate plasma concentration of GSK2982772. Pharmacokinetic parameters including trough plasma concentration was determined using standard non-compartmental methods. |
| Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Pre-dose on Days 1, 8 and 43 | 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. |
| Percent Change From Baseline in C-Reactive Protein (CRP) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
| Percent Change From Baseline in Interleukin 6 (IL6) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
| Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
| Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
| Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
| Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Baseline (Day 1 pre-dose), Days 43 and 85 | 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\*\[(post-dose value minus Baseline value)/ Baseline value\]. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Joint Volume | Baseline (Day 1 pre-dose), Days 43 and 85 | Joint volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points. |
| Change From Baseline in Enhancing Volume | Baseline (Day 1 pre-dose), Days 43 and 85 | Enhancing volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points. |
Countries
Germany, Italy, Poland, Russia, Spain, United Kingdom
Participant flow
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.
Pre-assignment 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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo BID 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. | 3 |
| Placebo TID 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. | 15 |
| GSK2982772 60 mg BID 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. | 5 |
| GSK2982772 60 mg TID 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. | 28 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | Protocol defined stopping criteria | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo BID | Placebo TID | GSK2982772 60 mg BID | GSK2982772 60 mg TID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.3 Years STANDARD_DEVIATION 4.93 | 53.1 Years STANDARD_DEVIATION 7.8 | 53.6 Years STANDARD_DEVIATION 7.86 | 55.0 Years STANDARD_DEVIATION 11.25 | 54.2 Years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 3 Participants | 15 Participants | 5 Participants | 27 Participants | 50 Participants |
| Sex: Female, Male Female | 2 Participants | 13 Participants | 4 Participants | 23 Participants | 42 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 15 | 0 / 5 | 0 / 28 |
| other Total, other adverse events | 3 / 3 | 10 / 15 | 3 / 5 | 16 / 28 |
| serious Total, serious adverse events | 0 / 3 | 0 / 15 | 0 / 5 | 2 / 28 |
Outcome results
Primary
Change From Baseline in Body Temperature at Indicated Time Points
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.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 8; n=3,15,5,25 | 0.60 Degrees Celsius | Standard Deviation 0.529 |
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 71; n=3,14,5,23 | 0.27 Degrees Celsius | Standard Deviation 0.404 |
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 57; n=3,14,5,23 | 0.53 Degrees Celsius | Standard Deviation 0.462 |
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 15; n=3,15,5,25 | 0.80 Degrees Celsius | Standard Deviation 0.5 |
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 85; n=3,14,5,22 | 0.53 Degrees Celsius | Standard Deviation 0.379 |
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 29; n=3,15,5,24 | 0.60 Degrees Celsius | Standard Deviation 0.656 |
| Placebo BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 43; n=3,14,5,24 | 0.53 Degrees Celsius | Standard Deviation 0.513 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 71; n=3,14,5,23 | -0.06 Degrees Celsius | Standard Deviation 0.21 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 43; n=3,14,5,24 | -0.01 Degrees Celsius | Standard Deviation 0.251 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 29; n=3,15,5,24 | -0.02 Degrees Celsius | Standard Deviation 0.204 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 57; n=3,14,5,23 | -0.02 Degrees Celsius | Standard Deviation 0.226 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 85; n=3,14,5,22 | -0.10 Degrees Celsius | Standard Deviation 0.162 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 15; n=3,15,5,25 | -0.07 Degrees Celsius | Standard Deviation 0.171 |
| Placebo TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 8; n=3,15,5,25 | -0.03 Degrees Celsius | Standard Deviation 0.209 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 43; n=3,14,5,24 | 0.04 Degrees Celsius | Standard Deviation 0.27 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 8; n=3,15,5,25 | -0.06 Degrees Celsius | Standard Deviation 0.261 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 15; n=3,15,5,25 | -0.04 Degrees Celsius | Standard Deviation 0.219 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 29; n=3,15,5,24 | 0.10 Degrees Celsius | Standard Deviation 0.187 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 57; n=3,14,5,23 | -0.02 Degrees Celsius | Standard Deviation 0.239 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 71; n=3,14,5,23 | -0.00 Degrees Celsius | Standard Deviation 0.141 |
| GSK2982772 60 mg BID | Change From Baseline in Body Temperature at Indicated Time Points | Day 85; n=3,14,5,22 | -0.12 Degrees Celsius | Standard Deviation 0.356 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 29; n=3,15,5,24 | 0.11 Degrees Celsius | Standard Deviation 0.249 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 85; n=3,14,5,22 | 0.14 Degrees Celsius | Standard Deviation 0.353 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 71; n=3,14,5,23 | 0.17 Degrees Celsius | Standard Deviation 0.255 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 15; n=3,15,5,25 | 0.06 Degrees Celsius | Standard Deviation 0.251 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 8; n=3,15,5,25 | 0.06 Degrees Celsius | Standard Deviation 0.222 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 57; n=3,14,5,23 | 0.16 Degrees Celsius | Standard Deviation 0.31 |
| GSK2982772 60 mg TID | Change From Baseline in Body Temperature at Indicated Time Points | Day 43; n=3,14,5,24 | 0.06 Degrees Celsius | Standard Deviation 0.286 |
Primary
Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points
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.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 15; n=3,14,5,24 | -3.3 Millisecond | Standard Deviation 4.16 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 29; n=2,14,5,21 | -2.4 Millisecond | Standard Deviation 7.96 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 57; n=2,13,5,21 | 5.9 Millisecond | Standard Deviation 11.57 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 43; n=2,13,5,22 | -13.0 Millisecond | Standard Deviation 14.51 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 85; n=3,13,5,21 | 1.3 Millisecond | Standard Deviation 10.02 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 57; n=2,13,5,21 | -1.5 Millisecond | Standard Deviation 1.83 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 85; n=2,13,5,20 | 4.2 Millisecond | Standard Deviation 15.78 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 43; n=3,13,5,23 | -3.3 Millisecond | Standard Deviation 5.51 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 43; n=2,13,5,22 | -13.5 Millisecond | Standard Deviation 23.4 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 8; n=2,14,5,22 | -16.0 Millisecond | Standard Deviation 3.35 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 15; n=2,14,5,23 | 7.5 Millisecond | Standard Deviation 7.65 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 57; n=3,13,5,22 | -12.0 Millisecond | Standard Deviation 5.29 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 29; n=2,14,5,21 | -3.3 Millisecond | Standard Deviation 13.16 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 57; n=3,13,5,22 | -6.0 Millisecond | Standard Deviation 6 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 71; n=2,13,5,21 | -9.3 Millisecond | Standard Deviation 16.59 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 71; n=3,13,5,22 | -10.0 Millisecond | Standard Deviation 7.55 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 43; n=3,13,5,23 | 2.0 Millisecond | Standard Deviation 17.35 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 85; n=3,13,5,21 | -7.3 Millisecond | Standard Deviation 11.37 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 8; n=3,14,5,23 | -25.7 Millisecond | Standard Deviation 6.11 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 8; n=3,14,5,23 | -4.7 Millisecond | Standard Deviation 5.03 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 29; n=3,14,5,22 | 5.3 Millisecond | Standard Deviation 24.01 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 15; n=3,14,5,24 | 2.7 Millisecond | Standard Deviation 11.02 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 29; n=3,14,5,22 | -9.3 Millisecond | Standard Deviation 17.67 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 15; n=3,14,5,24 | 6.3 Millisecond | Standard Deviation 12.66 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 43; n=3,13,5,23 | -12.7 Millisecond | Standard Deviation 28.1 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 57; n=3,13,5,22 | 12.3 Millisecond | Standard Deviation 30.04 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 8; n=3,14,5,23 | -0.3 Millisecond | Standard Deviation 14.36 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 71; n=3,13,5,22 | -9.3 Millisecond | Standard Deviation 33.98 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 85; n=2,13,5,20 | 2.5 Millisecond | Standard Deviation 17.46 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 85; n=3,13,5,21 | -0.3 Millisecond | Standard Deviation 14.5 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 8; n=2,14,5,22 | -12.1 Millisecond | Standard Deviation 8.34 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 71; n=3,13,5,22 | 1.0 Millisecond | Standard Deviation 17.78 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 71; n=2,13,5,21 | -11.1 Millisecond | Standard Deviation 27.3 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 15; n=2,14,5,23 | 7.2 Millisecond | Standard Deviation 7.18 |
| Placebo BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 29; n=3,14,5,22 | -1.3 Millisecond | Standard Deviation 3.79 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 57; n=2,13,5,21 | 9.6 Millisecond | Standard Deviation 38.25 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 8; n=3,14,5,23 | 6.4 Millisecond | Standard Deviation 40.17 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 29; n=2,14,5,21 | 4.4 Millisecond | Standard Deviation 25.73 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 29; n=3,14,5,22 | -2.1 Millisecond | Standard Deviation 10.89 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 57; n=3,13,5,22 | -4.0 Millisecond | Standard Deviation 5.9 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 71; n=2,13,5,21 | 7.6 Millisecond | Standard Deviation 30.12 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 43; n=2,13,5,22 | 9.1 Millisecond | Standard Deviation 37.18 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 71; n=3,13,5,22 | 13.8 Millisecond | Standard Deviation 32.5 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 15; n=3,14,5,24 | 20.7 Millisecond | Standard Deviation 34.85 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 71; n=2,13,5,21 | 4.6 Millisecond | Standard Deviation 34.77 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 57; n=3,13,5,22 | 5.8 Millisecond | Standard Deviation 21.75 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 43; n=2,13,5,22 | 12.4 Millisecond | Standard Deviation 35.37 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 8; n=3,14,5,23 | -3.3 Millisecond | Standard Deviation 10.75 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 85; n=2,13,5,20 | 7.0 Millisecond | Standard Deviation 32.09 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 15; n=3,14,5,24 | 0.6 Millisecond | Standard Deviation 29.94 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 15; n=3,14,5,24 | -3.1 Millisecond | Standard Deviation 10.5 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 29; n=3,14,5,22 | 7.6 Millisecond | Standard Deviation 25.03 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 8; n=2,14,5,22 | 9.0 Millisecond | Standard Deviation 42.58 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 43; n=3,13,5,23 | -1.1 Millisecond | Standard Deviation 9.9 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 29; n=2,14,5,21 | 5.6 Millisecond | Standard Deviation 22.87 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 57; n=2,13,5,21 | 7.5 Millisecond | Standard Deviation 38.73 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 15; n=2,14,5,23 | 22.2 Millisecond | Standard Deviation 39.68 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 15; n=2,14,5,23 | 22.9 Millisecond | Standard Deviation 46.1 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 8; n=2,14,5,22 | 10.5 Millisecond | Standard Deviation 46.28 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 43; n=3,13,5,23 | 18.5 Millisecond | Standard Deviation 38.73 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 71; n=3,13,5,22 | 1.2 Millisecond | Standard Deviation 18.65 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 43; n=3,13,5,23 | 6.5 Millisecond | Standard Deviation 14.44 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 8; n=3,14,5,23 | -1.9 Millisecond | Standard Deviation 26.35 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 71; n=3,13,5,22 | -0.2 Millisecond | Standard Deviation 6.68 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 85; n=2,13,5,20 | 10.6 Millisecond | Standard Deviation 28.46 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 85; n=3,13,5,21 | 17.2 Millisecond | Standard Deviation 32.16 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 57; n=3,13,5,22 | 13.6 Millisecond | Standard Deviation 41.48 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 85; n=3,13,5,21 | -1.0 Millisecond | Standard Deviation 9.07 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 85; n=3,13,5,21 | 6.2 Millisecond | Standard Deviation 15.38 |
| Placebo TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 29; n=3,14,5,22 | -3.5 Millisecond | Standard Deviation 32.15 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 43; n=3,13,5,23 | 3.6 Millisecond | Standard Deviation 8.29 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 57; n=2,13,5,21 | -7.0 Millisecond | Standard Deviation 11.67 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 85; n=2,13,5,20 | -7.0 Millisecond | Standard Deviation 11.36 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 8; n=3,14,5,23 | 8.2 Millisecond | Standard Deviation 10.33 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 15; n=3,14,5,24 | -1.2 Millisecond | Standard Deviation 7.26 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 29; n=3,14,5,22 | 0.4 Millisecond | Standard Deviation 5.03 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 57; n=3,13,5,22 | 3.2 Millisecond | Standard Deviation 9.34 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 71; n=3,13,5,22 | 4.6 Millisecond | Standard Deviation 12.26 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 85; n=3,13,5,21 | 3.4 Millisecond | Standard Deviation 8.68 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 8; n=3,14,5,23 | -14.2 Millisecond | Standard Deviation 22.49 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 15; n=3,14,5,24 | 0.0 Millisecond | Standard Deviation 21.12 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 29; n=3,14,5,22 | -5.6 Millisecond | Standard Deviation 22.37 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 43; n=3,13,5,23 | 1.0 Millisecond | Standard Deviation 20.74 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 57; n=3,13,5,22 | 2.4 Millisecond | Standard Deviation 22.78 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 71; n=3,13,5,22 | 10.2 Millisecond | Standard Deviation 28.71 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 85; n=3,13,5,21 | -3.2 Millisecond | Standard Deviation 14.6 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 8; n=2,14,5,22 | -10.3 Millisecond | Standard Deviation 14.09 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 15; n=2,14,5,23 | -12.9 Millisecond | Standard Deviation 17.59 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 29; n=2,14,5,21 | -21.2 Millisecond | Standard Deviation 29.58 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 43; n=2,13,5,22 | -14.2 Millisecond | Standard Deviation 14.64 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 71; n=2,13,5,21 | -11.0 Millisecond | Standard Deviation 16.47 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 85; n=2,13,5,20 | -9.1 Millisecond | Standard Deviation 12.42 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 8; n=2,14,5,22 | -11.4 Millisecond | Standard Deviation 14.05 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 15; n=2,14,5,23 | -8.4 Millisecond | Standard Deviation 18 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 29; n=2,14,5,21 | -15.6 Millisecond | Standard Deviation 18.24 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 43; n=2,13,5,22 | -8.7 Millisecond | Standard Deviation 13.81 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 57; n=2,13,5,21 | -3.5 Millisecond | Standard Deviation 11.35 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 71; n=2,13,5,21 | -3.5 Millisecond | Standard Deviation 18.48 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 8; n=3,14,5,23 | -6.4 Millisecond | Standard Deviation 19.98 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 15; n=3,14,5,24 | -2.0 Millisecond | Standard Deviation 23.1 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 29; n=3,14,5,22 | -0.2 Millisecond | Standard Deviation 22.66 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 43; n=3,13,5,23 | 2.4 Millisecond | Standard Deviation 5.41 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 57; n=3,13,5,22 | 5.0 Millisecond | Standard Deviation 6.36 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 71; n=3,13,5,22 | 2.2 Millisecond | Standard Deviation 23.92 |
| GSK2982772 60 mg BID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 85; n=3,13,5,21 | -0.2 Millisecond | Standard Deviation 5.26 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 57; n=2,13,5,21 | -0.1 Millisecond | Standard Deviation 42.41 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 8; n=2,14,5,22 | 0.7 Millisecond | Standard Deviation 33.2 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 85; n=3,13,5,21 | 3.0 Millisecond | Standard Deviation 17.28 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 15; n=3,14,5,24 | 1.1 Millisecond | Standard Deviation 6.89 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 71; n=2,13,5,21 | -1.2 Millisecond | Standard Deviation 17.15 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 71; n=3,13,5,22 | -2.1 Millisecond | Standard Deviation 22.06 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 85; n=2,13,5,20 | 0.6 Millisecond | Standard Deviation 12.45 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 57; n=3,13,5,22 | -1.8 Millisecond | Standard Deviation 36.44 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 43; n=3,13,5,23 | 0.6 Millisecond | Standard Deviation 29.36 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 8; n=3,14,5,23 | 3.7 Millisecond | Standard Deviation 12.97 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 8; n=3,14,5,23 | 0.8 Millisecond | Standard Deviation 18.84 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 29; n=3,14,5,22 | 5.5 Millisecond | Standard Deviation 31.49 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 15; n=3,14,5,24 | -4.5 Millisecond | Standard Deviation 25.27 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 85; n=3,13,5,21 | 0.4 Millisecond | Standard Deviation 10.29 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 15; n=3,14,5,24 | 3.0 Millisecond | Standard Deviation 15.71 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QT interval; Day 8; n=3,14,5,23 | -1.0 Millisecond | Standard Deviation 35.97 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 85; n=3,13,5,21 | 1.5 Millisecond | Standard Deviation 10.68 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 71; n=3,13,5,22 | 0.8 Millisecond | Standard Deviation 15.06 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 29; n=3,14,5,22 | -6.9 Millisecond | Standard Deviation 28 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 71; n=3,13,5,22 | -0.5 Millisecond | Standard Deviation 8.31 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 57; n=3,13,5,22 | 1.0 Millisecond | Standard Deviation 18.33 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 57; n=2,13,5,21 | 1.1 Millisecond | Standard Deviation 47.85 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 43; n=3,13,5,23 | 6.6 Millisecond | Standard Deviation 15.69 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 43; n=3,13,5,23 | 0.3 Millisecond | Standard Deviation 10.48 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 15; n=2,14,5,23 | -2.3 Millisecond | Standard Deviation 17.61 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 8; n=2,14,5,22 | 0.3 Millisecond | Standard Deviation 33.04 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QRS duration; Day 29; n=3,14,5,22 | -0.5 Millisecond | Standard Deviation 9.01 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 29; n=2,14,5,21 | 8.7 Millisecond | Standard Deviation 27.77 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 85; n=2,13,5,20 | -0.7 Millisecond | Standard Deviation 17.51 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 71; n=2,13,5,21 | -1.1 Millisecond | Standard Deviation 20.55 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 43; n=2,13,5,22 | 0.6 Millisecond | Standard Deviation 27.77 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcF; Day 43; n=2,13,5,22 | 0.7 Millisecond | Standard Deviation 25.16 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 29; n=2,14,5,21 | 10.3 Millisecond | Standard Deviation 29.02 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | QTcB; Day 15; n=2,14,5,23 | -0.9 Millisecond | Standard Deviation 19.63 |
| GSK2982772 60 mg TID | Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time Points | PR interval; Day 57; n=3,13,5,22 | 4.1 Millisecond | Standard Deviation 17.51 |
Primary
Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points
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.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 8; n=3,14,5,23 | 7.0 Beats per minute | Standard Deviation 5.57 |
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 71; n=3,13,5,22 | 0.3 Beats per minute | Standard Deviation 9.29 |
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 57; n=3,13,5,22 | -3.7 Beats per minute | Standard Deviation 10.69 |
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 15; n=3,14,5,24 | 0.7 Beats per minute | Standard Deviation 2.08 |
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 85; n=3,13,5,21 | -1.7 Beats per minute | Standard Deviation 5.69 |
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 29; n=3,14,5,22 | 2.7 Beats per minute | Standard Deviation 4.93 |
| Placebo BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 43; n=3,13,5,23 | -0.7 Beats per minute | Standard Deviation 7.57 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 71; n=3,13,5,22 | -3.0 Beats per minute | Standard Deviation 12.08 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 43; n=3,13,5,23 | -3.5 Beats per minute | Standard Deviation 9.73 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 29; n=3,14,5,22 | -1.4 Beats per minute | Standard Deviation 8.27 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 57; n=3,13,5,22 | -2.4 Beats per minute | Standard Deviation 8.79 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 85; n=3,13,5,21 | -4.1 Beats per minute | Standard Deviation 11.51 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 15; n=3,14,5,24 | -0.3 Beats per minute | Standard Deviation 11.64 |
| Placebo TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 8; n=3,14,5,23 | 1.1 Beats per minute | Standard Deviation 10.68 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 43; n=3,13,5,23 | -6.0 Beats per minute | Standard Deviation 7.35 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 8; n=3,14,5,23 | 0.6 Beats per minute | Standard Deviation 7.09 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 15; n=3,14,5,24 | -4.6 Beats per minute | Standard Deviation 4.16 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 29; n=3,14,5,22 | -5.8 Beats per minute | Standard Deviation 13.66 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 57; n=3,13,5,22 | -4.2 Beats per minute | Standard Deviation 8.58 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 71; n=3,13,5,22 | -7.6 Beats per minute | Standard Deviation 7.73 |
| GSK2982772 60 mg BID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 85; n=3,13,5,21 | -2.4 Beats per minute | Standard Deviation 4.72 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 29; n=3,14,5,22 | 1.3 Beats per minute | Standard Deviation 9.14 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 85; n=3,13,5,21 | -1.4 Beats per minute | Standard Deviation 9.12 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 71; n=3,13,5,22 | 0.3 Beats per minute | Standard Deviation 9.32 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 15; n=3,14,5,24 | 1.0 Beats per minute | Standard Deviation 9.94 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 8; n=3,14,5,23 | 0.6 Beats per minute | Standard Deviation 7.55 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 57; n=3,13,5,22 | 0.7 Beats per minute | Standard Deviation 9.75 |
| GSK2982772 60 mg TID | Change From Baseline in Electrocardiogram (ECG) Heart Rate at Indicated Time Points | Day 43; n=3,13,5,23 | -0.2 Beats per minute | Standard Deviation 10.86 |
Primary
Change From Baseline in Respiratory Rate at Indicated Time Points
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.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 85; n=3,14,5,22 | 0.7 Breaths per minute | Standard Deviation 0.58 |
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 43; n=3,14,5,24 | 1.7 Breaths per minute | Standard Deviation 0.58 |
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 29; n=3,15,5,24 | 1.0 Breaths per minute | Standard Deviation 1 |
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 71; n=3,14,5,23 | 1.7 Breaths per minute | Standard Deviation 0.58 |
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 57; n=3,14,5,23 | 1.7 Breaths per minute | Standard Deviation 2.08 |
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 15; n=3,15,5,25 | 1.0 Breaths per minute | Standard Deviation 1.73 |
| Placebo BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 8; n=3,15,5,25 | 0.7 Breaths per minute | Standard Deviation 1.53 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 43; n=3,14,5,24 | 0.3 Breaths per minute | Standard Deviation 1.33 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 8; n=3,15,5,25 | 0.1 Breaths per minute | Standard Deviation 1.13 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 15; n=3,15,5,25 | 0.2 Breaths per minute | Standard Deviation 1.08 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 29; n=3,15,5,24 | -0.2 Breaths per minute | Standard Deviation 1.47 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 57; n=3,14,5,23 | 0.2 Breaths per minute | Standard Deviation 0.7 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 71; n=3,14,5,23 | 0.5 Breaths per minute | Standard Deviation 0.65 |
| Placebo TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 85; n=3,14,5,22 | 0.4 Breaths per minute | Standard Deviation 0.84 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 15; n=3,15,5,25 | -1.2 Breaths per minute | Standard Deviation 1.79 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 43; n=3,14,5,24 | -0.8 Breaths per minute | Standard Deviation 1.1 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 57; n=3,14,5,23 | 0.4 Breaths per minute | Standard Deviation 3.29 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 8; n=3,15,5,25 | -0.4 Breaths per minute | Standard Deviation 2.61 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 85; n=3,14,5,22 | -0.4 Breaths per minute | Standard Deviation 2.61 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 71; n=3,14,5,23 | 0.0 Breaths per minute | Standard Deviation 2.45 |
| GSK2982772 60 mg BID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 29; n=3,15,5,24 | -1.6 Breaths per minute | Standard Deviation 1.67 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 71; n=3,14,5,23 | 0.7 Breaths per minute | Standard Deviation 2.07 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 15; n=3,15,5,25 | 0.2 Breaths per minute | Standard Deviation 1.91 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 43; n=3,14,5,24 | 0.5 Breaths per minute | Standard Deviation 2.7 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 8; n=3,15,5,25 | 0.0 Breaths per minute | Standard Deviation 1.14 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 85; n=3,14,5,22 | 0.5 Breaths per minute | Standard Deviation 1.6 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 29; n=3,15,5,24 | 0.1 Breaths per minute | Standard Deviation 1.28 |
| GSK2982772 60 mg TID | Change From Baseline in Respiratory Rate at Indicated Time Points | Day 57; n=3,14,5,23 | 0.6 Breaths per minute | Standard Deviation 2 |
Primary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
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.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 15; n=3,15,5,25 | 0.3 Millimeters of Mercury (mmHg) | Standard Deviation 6.11 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 8; n=3,15,5,25 | 2.00 Millimeters of Mercury (mmHg) | Standard Deviation 5 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 57; n=3,14,5,23 | -14.7 Millimeters of Mercury (mmHg) | Standard Deviation 17.21 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 85; n=3,14,5,22 | 1.0 Millimeters of Mercury (mmHg) | Standard Deviation 6.24 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 85; n=3,14,5,22 | -4.3 Millimeters of Mercury (mmHg) | Standard Deviation 12.7 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 71; n=3,14,5,23 | -7.0 Millimeters of Mercury (mmHg) | Standard Deviation 9.85 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 57; n=3,14,5,23 | -3.7 Millimeters of Mercury (mmHg) | Standard Deviation 8.33 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 8; n=3,15,5,25 | -9.7 Millimeters of Mercury (mmHg) | Standard Deviation 5.69 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 29; n=3,15,5,24 | -9.3 Millimeters of Mercury (mmHg) | Standard Deviation 15.7 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 71; n=3,14,5,23 | -7.0 Millimeters of Mercury (mmHg) | Standard Deviation 9.17 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 43; n=3,14,5,24 | 0.3 Millimeters of Mercury (mmHg) | Standard Deviation 14.36 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 29; n=3,15,5,24 | -4.0 Millimeters of Mercury (mmHg) | Standard Deviation 8.89 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 43; n=3,14,5,24 | -7.0 Millimeters of Mercury (mmHg) | Standard Deviation 9.54 |
| Placebo BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 15; n=3,15,5,25 | -2.0 Millimeters of Mercury (mmHg) | Standard Deviation 7.55 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 43; n=3,14,5,24 | -0.3 Millimeters of Mercury (mmHg) | Standard Deviation 8.96 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 8; n=3,15,5,25 | 0.5 Millimeters of Mercury (mmHg) | Standard Deviation 12.61 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 15; n=3,15,5,25 | -2.7 Millimeters of Mercury (mmHg) | Standard Deviation 11.21 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 29; n=3,15,5,24 | -0.8 Millimeters of Mercury (mmHg) | Standard Deviation 10.82 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 43; n=3,14,5,24 | -2.0 Millimeters of Mercury (mmHg) | Standard Deviation 15.11 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 57; n=3,14,5,23 | 0.5 Millimeters of Mercury (mmHg) | Standard Deviation 16.19 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 71; n=3,14,5,23 | 1.1 Millimeters of Mercury (mmHg) | Standard Deviation 14.35 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 85; n=3,14,5,22 | -0.1 Millimeters of Mercury (mmHg) | Standard Deviation 14.68 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 8; n=3,15,5,25 | 2.0 Millimeters of Mercury (mmHg) | Standard Deviation 11.32 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 15; n=3,15,5,25 | 0.3 Millimeters of Mercury (mmHg) | Standard Deviation 7.85 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 29; n=3,15,5,24 | 0.2 Millimeters of Mercury (mmHg) | Standard Deviation 8.28 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 57; n=3,14,5,23 | 0.8 Millimeters of Mercury (mmHg) | Standard Deviation 9.9 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 71; n=3,14,5,23 | 1.4 Millimeters of Mercury (mmHg) | Standard Deviation 8.36 |
| Placebo TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 85; n=3,14,5,22 | 2.1 Millimeters of Mercury (mmHg) | Standard Deviation 10.79 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 43; n=3,14,5,24 | -1.4 Millimeters of Mercury (mmHg) | Standard Deviation 8.76 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 71; n=3,14,5,23 | -7.2 Millimeters of Mercury (mmHg) | Standard Deviation 9.76 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 15; n=3,15,5,25 | -13.0 Millimeters of Mercury (mmHg) | Standard Deviation 12.79 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 43; n=3,14,5,24 | -11.4 Millimeters of Mercury (mmHg) | Standard Deviation 19.72 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 57; n=3,14,5,23 | 1.4 Millimeters of Mercury (mmHg) | Standard Deviation 6.43 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 8; n=3,15,5,25 | -4.6 Millimeters of Mercury (mmHg) | Standard Deviation 14.33 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 29; n=3,15,5,24 | -2.0 Millimeters of Mercury (mmHg) | Standard Deviation 6.04 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 8; n=3,15,5,25 | 1.0 Millimeters of Mercury (mmHg) | Standard Deviation 8.69 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 71; n=3,14,5,23 | -8.2 Millimeters of Mercury (mmHg) | Standard Deviation 12.19 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 29; n=3,15,5,24 | -8.2 Millimeters of Mercury (mmHg) | Standard Deviation 19.12 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 57; n=3,14,5,23 | -9.6 Millimeters of Mercury (mmHg) | Standard Deviation 18.49 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 85; n=3,14,5,22 | -1.4 Millimeters of Mercury (mmHg) | Standard Deviation 7.67 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 85; n=3,14,5,22 | -4.8 Millimeters of Mercury (mmHg) | Standard Deviation 11.23 |
| GSK2982772 60 mg BID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 15; n=3,15,5,25 | 0.4 Millimeters of Mercury (mmHg) | Standard Deviation 4.39 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 85; n=3,14,5,22 | 1.9 Millimeters of Mercury (mmHg) | Standard Deviation 12.97 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 8; n=3,15,5,25 | -0.4 Millimeters of Mercury (mmHg) | Standard Deviation 7.12 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 71; n=3,14,5,23 | -1.5 Millimeters of Mercury (mmHg) | Standard Deviation 6.9 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 15; n=3,15,5,25 | 1.1 Millimeters of Mercury (mmHg) | Standard Deviation 7.61 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 29; n=3,15,5,24 | 1.9 Millimeters of Mercury (mmHg) | Standard Deviation 11.94 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 29; n=3,15,5,24 | 0.7 Millimeters of Mercury (mmHg) | Standard Deviation 7.65 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 15; n=3,15,5,25 | 4.6 Millimeters of Mercury (mmHg) | Standard Deviation 9.43 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 43; n=3,14,5,24 | -0.8 Millimeters of Mercury (mmHg) | Standard Deviation 6.68 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 85; n=3,14,5,22 | -0.4 Millimeters of Mercury (mmHg) | Standard Deviation 7.5 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | DBP; Day 57; n=3,14,5,23 | -0.9 Millimeters of Mercury (mmHg) | Standard Deviation 7.78 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 57; n=3,14,5,23 | -0.3 Millimeters of Mercury (mmHg) | Standard Deviation 12.84 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 8; n=3,15,5,25 | 2.7 Millimeters of Mercury (mmHg) | Standard Deviation 11 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 71; n=3,14,5,23 | 1.2 Millimeters of Mercury (mmHg) | Standard Deviation 14.4 |
| GSK2982772 60 mg TID | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points | SBP; Day 43; n=3,14,5,24 | -1.6 Millimeters of Mercury (mmHg) | Standard Deviation 10.01 |
Primary
Change From Baseline in Vital Sign-heart Rate at Indicated Time Points
Vital sign-heart rate was planned to be assessed as a measure of safety and tolerability.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 29, 43, 57, 71 and 85
Population: The data for assessment of vital sign-heart rate was not collected.
Primary
Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
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.
Time frame: Up to Day 112
Population: Safety Population comprised of all participants who received at least one dose of the study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any nSAEs | 3 Participants |
| Placebo BID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any SAEs | 0 Participants |
| Placebo TID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any SAEs | 0 Participants |
| Placebo TID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any nSAEs | 10 Participants |
| GSK2982772 60 mg BID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any nSAEs | 3 Participants |
| GSK2982772 60 mg BID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any SAEs | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any nSAEs | 16 Participants |
| GSK2982772 60 mg TID | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Any SAEs | 2 Participants |
Primary
Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
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.
Time frame: Up to Day 112
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose; Any increase | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones; Any increase | 1 Participants |
| Placebo BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood; Any increase | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein; Any increase | 1 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones; Any increase | 3 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood; Any increase | 6 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein; Any increase | 2 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose; Any increase | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood; Any increase | 1 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones; Any increase | 3 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein; Any increase | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose; Any increase | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein; Any increase | 6 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones; Any increase | 6 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose; Any increase | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood; Any increase | 8 Participants |
Primary
Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method
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.
Time frame: Up to Day 112
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | White blood cells;any increase;n=2,7,1,11 | 2 Participants |
| Placebo BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | Red blood cells;any increase;n=2,7,1,11 | 1 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | White blood cells;any increase;n=2,7,1,11 | 5 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | Red blood cells;any increase;n=2,7,1,11 | 5 Participants |
| Placebo TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | Hyaline casts;any increase;n=0,1,0,0 | 1 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | Red blood cells;any increase;n=2,7,1,11 | 1 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | White blood cells;any increase;n=2,7,1,11 | 1 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | White blood cells;any increase;n=2,7,1,11 | 7 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Microscopy Method | Red blood cells;any increase;n=2,7,1,11 | 8 Participants |
Primary
Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI)
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.
Time frame: Up to Day 112
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To Low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To low | 1 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To high | 1 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To Low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To Low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Calcium; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To high | 1 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To high | 1 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | AST; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To high | 2 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Alkaline phosphatase; To Low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | ALT; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Sodium; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Albumin; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Glucose; To high | 1 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Creatinine; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Total bilirubin; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Clinical Chemistry Parameters of Potential Clinical Importance (PCI) | Potassium; To low | 0 Participants |
Primary
Number of Participants With Worst Case Hematology Parameters of PCI
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.
Time frame: Up to Day 112
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To low | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To Low | 2 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To high | 0 Participants |
| Placebo BID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To high | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To Low | 1 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To low | 0 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To high | 1 Participants |
| Placebo TID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To Low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To high | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To low | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Lymphocytes; To Low | 1 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hemoglobin; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | WBC; To low | 1 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Platelet count; To low | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Hematocrit; To high | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants With Worst Case Hematology Parameters of PCI | Total neutrophils; To low | 1 Participants |
Secondary
Change From Baseline in Bone Edema by Modified CARLOS
Change from Baseline in bone edema was planned to be assessed by modified CARLOS.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Data was not collected for this outcome measure, as bone edema is not a part of modified CARLOS. Bone edema was measured by OMERACT-RAMRIS and RAMRIQ scoring system and is presented in outcome measures 29 and 30, respectively.
Secondary
Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | -1.0 Scores on a scale | Standard Deviation 1.73 |
| Placebo BID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | 0.3 Scores on a scale | Standard Deviation 0.58 |
| Placebo TID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | 0.3 Scores on a scale | Standard Deviation 1.38 |
| Placebo TID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | -0.2 Scores on a scale | Standard Deviation 1.52 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | -0.8 Scores on a scale | Standard Deviation 3.27 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | -4.4 Scores on a scale | Standard Deviation 6.8 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | -0.9 Scores on a scale | Standard Deviation 2.47 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Edema by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | -1.1 Scores on a scale | Standard Deviation 2.59 |
Secondary
Change From Baseline in Bone Edema by RAMRIQ Scoring System
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 43;n=2,13,5,22 | -0.00396 Scores on a scale | Standard Deviation 0.000647 |
| Placebo BID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | 0.00116 Scores on a scale | Standard Deviation 0.010166 |
| Placebo TID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.00229 Scores on a scale | Standard Deviation 0.010143 |
| Placebo TID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 43;n=2,13,5,22 | -0.00463 Scores on a scale | Standard Deviation 0.007465 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 43;n=2,13,5,22 | -0.01963 Scores on a scale | Standard Deviation 0.031481 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.03921 Scores on a scale | Standard Deviation 0.055431 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 43;n=2,13,5,22 | -0.00095 Scores on a scale | Standard Deviation 0.018745 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Edema by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.00384 Scores on a scale | Standard Deviation 0.016126 |
Secondary
Change From Baseline in Bone Erosions by Modified Cartilage Loss Scoring System (CARLOS)
Change from Baseline in bone erosions was planned to be assessed by modified CARLOS.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Data was not collected for this outcome measure, as bone erosion is not a part of modified CARLOS. Bone erosion was measured by OMERACT-RAMRIS and RAMRIQ scoring system and is presented in outcome measures 23 and 24, respectively.
Secondary
Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 43;n=2,13,5,23 | -0.00160 Scores on a scale | Standard Deviation 0.00255 |
| Placebo BID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 85;n=2,13,5,21 | -0.00069 Scores on a scale | Standard Deviation 0.001134 |
| Placebo TID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 85;n=2,13,5,21 | -0.00075 Scores on a scale | Standard Deviation 0.001301 |
| Placebo TID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 43;n=2,13,5,23 | -0.00110 Scores on a scale | Standard Deviation 0.002265 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 85;n=2,13,5,21 | -0.00273 Scores on a scale | Standard Deviation 0.003505 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 43;n=2,13,5,23 | -0.00072 Scores on a scale | Standard Deviation 0.001662 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 85;n=2,13,5,21 | 0.00059 Scores on a scale | Standard Deviation 0.003946 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Erosions by the Rheumatoid Arthritis MRI Quantitative (RAMRIQ) Scoring System | Day 43;n=2,13,5,23 | -0.00069 Scores on a scale | Standard Deviation 0.004145 |
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
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 43;n=3,13,5,24 | 0.7 Scores on a scale | Standard Deviation 1.15 |
| Placebo BID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 85;n=3,13,5,22 | 1.7 Scores on a scale | Standard Deviation 2.89 |
| Placebo TID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 43;n=3,13,5,24 | 0.6 Scores on a scale | Standard Deviation 1.04 |
| Placebo TID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 85;n=3,13,5,22 | 1.3 Scores on a scale | Standard Deviation 2.43 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 85;n=3,13,5,22 | 0.4 Scores on a scale | Standard Deviation 1.52 |
| GSK2982772 60 mg BID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 43;n=3,13,5,24 | 0.4 Scores on a scale | Standard Deviation 1.52 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 43;n=3,13,5,24 | -0.2 Scores on a scale | Standard Deviation 1.83 |
| GSK2982772 60 mg TID | Change From Baseline in Bone Erosion Total Score by Outcome Measures in Rheumatology, Rheumatoid Arthritis Magnetic Resonance Image Scoring System (OMERACT-RAMRIS) Scoring System | Day 85;n=3,13,5,22 | -0.1 Scores on a scale | Standard Deviation 2.21 |
Secondary
Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) Scores
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.
Time frame: Baseline (Day 1 pre-dose) and Day 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo BID | Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) Scores | -1.00 Scores on a scale |
| Placebo TID | Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) Scores | -0.87 Scores on a scale |
| GSK2982772 60 mg BID | Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) Scores | -1.47 Scores on a scale |
| GSK2982772 60 mg TID | Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP) Scores | -1.23 Scores on a scale |
Secondary
Change From Baseline in Exchange Rate (Ktrans)
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Exchange Rate (Ktrans) | Day 43;n=2,9,5,19 | 0.0012 Per minute | Standard Deviation 0.00076 |
| Placebo BID | Change From Baseline in Exchange Rate (Ktrans) | Day 85;n=2,9,5,17 | 0.0002 Per minute | Standard Deviation 0.01726 |
| Placebo TID | Change From Baseline in Exchange Rate (Ktrans) | Day 85;n=2,9,5,17 | -0.0021 Per minute | Standard Deviation 0.01385 |
| Placebo TID | Change From Baseline in Exchange Rate (Ktrans) | Day 43;n=2,9,5,19 | 0.0022 Per minute | Standard Deviation 0.01214 |
| GSK2982772 60 mg BID | Change From Baseline in Exchange Rate (Ktrans) | Day 43;n=2,9,5,19 | -0.0095 Per minute | Standard Deviation 0.01716 |
| GSK2982772 60 mg BID | Change From Baseline in Exchange Rate (Ktrans) | Day 85;n=2,9,5,17 | -0.0073 Per minute | Standard Deviation 0.00618 |
| GSK2982772 60 mg TID | Change From Baseline in Exchange Rate (Ktrans) | Day 43;n=2,9,5,19 | -0.0018 Per minute | Standard Deviation 0.01443 |
| GSK2982772 60 mg TID | Change From Baseline in Exchange Rate (Ktrans) | Day 85;n=2,9,5,17 | -0.0043 Per minute | Standard Deviation 0.01747 |
Secondary
Change From Baseline in Fractional Volume of Blood Plasma (Vp)
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 43;n=2,9,5,19 | 0.0018 Ratio of plasma volume to tissue volume | Standard Deviation 0.00166 |
| Placebo BID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 85;n=2,9,5,17 | 0.0000 Ratio of plasma volume to tissue volume | Standard Deviation 0.00019 |
| Placebo TID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 85;n=2,9,5,17 | -0.0022 Ratio of plasma volume to tissue volume | Standard Deviation 0.00407 |
| Placebo TID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 43;n=2,9,5,19 | 0.0007 Ratio of plasma volume to tissue volume | Standard Deviation 0.00678 |
| GSK2982772 60 mg BID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 43;n=2,9,5,19 | -0.0023 Ratio of plasma volume to tissue volume | Standard Deviation 0.00786 |
| GSK2982772 60 mg BID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 85;n=2,9,5,17 | -0.0001 Ratio of plasma volume to tissue volume | Standard Deviation 0.00272 |
| GSK2982772 60 mg TID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 43;n=2,9,5,19 | -0.0007 Ratio of plasma volume to tissue volume | Standard Deviation 0.00358 |
| GSK2982772 60 mg TID | Change From Baseline in Fractional Volume of Blood Plasma (Vp) | Day 85;n=2,9,5,17 | -0.0007 Ratio of plasma volume to tissue volume | Standard Deviation 0.00282 |
Secondary
Change From Baseline in Initial Rate of Enhancement (IRE)
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 43;n=2,9,5,19 | -0.00002 Millimole per second | Standard Deviation 0.000044 |
| Placebo BID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 85;n=2,9,5,17 | -0.00011 Millimole per second | Standard Deviation 0.000566 |
| Placebo TID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 85;n=2,9,5,17 | -0.00010 Millimole per second | Standard Deviation 0.000542 |
| Placebo TID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 43;n=2,9,5,19 | 0.00008 Millimole per second | Standard Deviation 0.000538 |
| GSK2982772 60 mg BID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 43;n=2,9,5,19 | -0.00043 Millimole per second | Standard Deviation 0.00075 |
| GSK2982772 60 mg BID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 85;n=2,9,5,17 | -0.00037 Millimole per second | Standard Deviation 0.000271 |
| GSK2982772 60 mg TID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 43;n=2,9,5,19 | -0.00008 Millimole per second | Standard Deviation 0.000575 |
| GSK2982772 60 mg TID | Change From Baseline in Initial Rate of Enhancement (IRE) | Day 85;n=2,9,5,17 | -0.00014 Millimole per second | Standard Deviation 0.000735 |
Secondary
Change From Baseline in Interstitial Volume (Ve)
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Interstitial Volume (Ve) | Day 43;n=2,9,5,18 | -0.305 Ratio of EC space to tissue volume | Standard Deviation 0.3128 |
| Placebo BID | Change From Baseline in Interstitial Volume (Ve) | Day 85;n=2,9,5,15 | 0.009 Ratio of EC space to tissue volume | Standard Deviation 0.784 |
| Placebo TID | Change From Baseline in Interstitial Volume (Ve) | Day 85;n=2,9,5,15 | -0.024 Ratio of EC space to tissue volume | Standard Deviation 0.245 |
| Placebo TID | Change From Baseline in Interstitial Volume (Ve) | Day 43;n=2,9,5,18 | -0.066 Ratio of EC space to tissue volume | Standard Deviation 0.3615 |
| GSK2982772 60 mg BID | Change From Baseline in Interstitial Volume (Ve) | Day 43;n=2,9,5,18 | -0.140 Ratio of EC space to tissue volume | Standard Deviation 0.4825 |
| GSK2982772 60 mg BID | Change From Baseline in Interstitial Volume (Ve) | Day 85;n=2,9,5,15 | -0.278 Ratio of EC space to tissue volume | Standard Deviation 0.517 |
| GSK2982772 60 mg TID | Change From Baseline in Interstitial Volume (Ve) | Day 43;n=2,9,5,18 | 0.073 Ratio of EC space to tissue volume | Standard Deviation 0.4044 |
| GSK2982772 60 mg TID | Change From Baseline in Interstitial Volume (Ve) | Day 85;n=2,9,5,15 | 0.113 Ratio of EC space to tissue volume | Standard Deviation 0.4664 |
Secondary
Change From Baseline in Joint Space Narrowing by Modified CARLOS
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 43;n=3,13,5,24 | 0.00 Scores on a scale | Standard Deviation 0 |
| Placebo BID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 85;n=3,13,5,22 | 0.00 Scores on a scale | Standard Deviation 0 |
| Placebo TID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 85;n=3,13,5,22 | 0.00 Scores on a scale | Standard Deviation 0 |
| Placebo TID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 43;n=3,13,5,24 | 0.00 Scores on a scale | Standard Deviation 0 |
| GSK2982772 60 mg BID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 43;n=3,13,5,24 | 0.00 Scores on a scale | Standard Deviation 0 |
| GSK2982772 60 mg BID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 85;n=3,13,5,22 | 0.00 Scores on a scale | Standard Deviation 0 |
| GSK2982772 60 mg TID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 43;n=3,13,5,24 | 0.08 Scores on a scale | Standard Deviation 0.408 |
| GSK2982772 60 mg TID | Change From Baseline in Joint Space Narrowing by Modified CARLOS | Day 85;n=3,13,5,22 | 0.09 Scores on a scale | Standard Deviation 0.426 |
Secondary
Change From Baseline in Joint Space Narrowing by OMERACT-RAMRIS Scoring System
Change from Baseline in joint space narrowing was planned to be assessed by OMERACT-RAMRIS scoring system.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Data was not collected for this outcome measure, as joint space narrowing is not a part of OMERACT-RAMRIS scoring system. Joint space narrowing was measured by RAMRIQ scoring system and modified CARLOS and is presented in outcome measures 33 and 34, respectively.
Secondary
Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | 1.121 Scores on a scale | Standard Deviation 1.4793 |
| Placebo BID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | 0.534 Scores on a scale | Standard Deviation 0.891 |
| Placebo TID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | 0.216 Scores on a scale | Standard Deviation 0.6974 |
| Placebo TID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | 0.378 Scores on a scale | Standard Deviation 1.3394 |
| GSK2982772 60 mg BID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | 0.484 Scores on a scale | Standard Deviation 2.898 |
| GSK2982772 60 mg BID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | 0.235 Scores on a scale | Standard Deviation 2.2525 |
| GSK2982772 60 mg TID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | -0.335 Scores on a scale | Standard Deviation 1.4365 |
| GSK2982772 60 mg TID | Change From Baseline in Joint Space Narrowing by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.433 Scores on a scale | Standard Deviation 1.1205 |
Secondary
Change From Baseline in Maximal Signal Intensity Enhancement (ME)
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 43;n=2,9,5,19 | -0.0300 Millimole | Standard Deviation 0.00994 |
| Placebo BID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 85;n=2,9,5,17 | -0.0533 Millimole | Standard Deviation 0.00473 |
| Placebo TID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 85;n=2,9,5,17 | -0.0138 Millimole | Standard Deviation 0.05168 |
| Placebo TID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 43;n=2,9,5,19 | 0.0029 Millimole | Standard Deviation 0.05405 |
| GSK2982772 60 mg BID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 43;n=2,9,5,19 | -0.0531 Millimole | Standard Deviation 0.06876 |
| GSK2982772 60 mg BID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 85;n=2,9,5,17 | -0.0584 Millimole | Standard Deviation 0.06009 |
| GSK2982772 60 mg TID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 43;n=2,9,5,19 | 0.0007 Millimole | Standard Deviation 0.06159 |
| GSK2982772 60 mg TID | Change From Baseline in Maximal Signal Intensity Enhancement (ME) | Day 85;n=2,9,5,17 | -0.0074 Millimole | Standard Deviation 0.0718 |
Secondary
Change From Baseline in Synovitis by Modified CARLOS
Change from Baseline in synovitis was planned to be assessed by modified CARLOS.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Data was not collected for this outcome measure, as synovitis is not a part of modified CARLOS. Synovitis was measured by OMERACT-RAMRIS and RAMRIQ scoring system and is presented in outcome measures 26 and 27, respectively.
Secondary
Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | 0.0 Scores on a scale | Standard Deviation 1.73 |
| Placebo BID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | 0.3 Scores on a scale | Standard Deviation 1.15 |
| Placebo TID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | 0.5 Scores on a scale | Standard Deviation 2.67 |
| Placebo TID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | 0.3 Scores on a scale | Standard Deviation 1.55 |
| GSK2982772 60 mg BID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | -0.4 Scores on a scale | Standard Deviation 1.52 |
| GSK2982772 60 mg BID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | -0.4 Scores on a scale | Standard Deviation 1.52 |
| GSK2982772 60 mg TID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 43;n=3,13,5,24 | -0.3 Scores on a scale | Standard Deviation 1.9 |
| GSK2982772 60 mg TID | Change From Baseline in Synovitis by OMERACT-RAMRIS Scoring System | Day 85;n=3,13,5,22 | -0.5 Scores on a scale | Standard Deviation 2.2 |
Secondary
Change From Baseline in Synovitis by RAMRIQ Scoring System
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.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | -0.0570 Scores on a scale | Standard Deviation 0.02302 |
| Placebo BID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.0659 Scores on a scale | Standard Deviation 0.01625 |
| Placebo TID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | 0.0251 Scores on a scale | Standard Deviation 0.12286 |
| Placebo TID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | -0.0165 Scores on a scale | Standard Deviation 0.04302 |
| GSK2982772 60 mg BID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | -0.0592 Scores on a scale | Standard Deviation 0.06931 |
| GSK2982772 60 mg BID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.0270 Scores on a scale | Standard Deviation 0.07061 |
| GSK2982772 60 mg TID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 43;n=2,13,5,23 | -0.0084 Scores on a scale | Standard Deviation 0.1049 |
| GSK2982772 60 mg TID | Change From Baseline in Synovitis by RAMRIQ Scoring System | Day 85;n=2,13,5,21 | -0.0107 Scores on a scale | Standard Deviation 0.11472 |
Secondary
Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response
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.
Time frame: Day 85
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR20 | 1 Participants |
| Placebo BID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR70 | 1 Participants |
| Placebo BID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR50 | 1 Participants |
| Placebo TID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR20 | 6 Participants |
| Placebo TID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR70 | 1 Participants |
| Placebo TID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR50 | 2 Participants |
| GSK2982772 60 mg BID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR50 | 0 Participants |
| GSK2982772 60 mg BID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR20 | 3 Participants |
| GSK2982772 60 mg BID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR70 | 0 Participants |
| GSK2982772 60 mg TID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR20 | 12 Participants |
| GSK2982772 60 mg TID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR70 | 4 Participants |
| GSK2982772 60 mg TID | Number of Participants Achieving Categorical American College of rheumatology20/50/70 (ACR20/50/70) Response | ACR50 | 5 Participants |
Secondary
Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response
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.
Time frame: Day 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo BID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | No response | 2 Participants |
| Placebo BID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Good response | 1 Participants |
| Placebo BID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Moderate response | 0 Participants |
| Placebo TID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | No response | 6 Participants |
| Placebo TID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Good response | 2 Participants |
| Placebo TID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Moderate response | 4 Participants |
| GSK2982772 60 mg BID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Moderate response | 2 Participants |
| GSK2982772 60 mg BID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | No response | 1 Participants |
| GSK2982772 60 mg BID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Good response | 2 Participants |
| GSK2982772 60 mg TID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | No response | 7 Participants |
| GSK2982772 60 mg TID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Good response | 7 Participants |
| GSK2982772 60 mg TID | Number of Participants Achieving Categorical DAS28-CRP Response Using European League Against Rheumatism [EULAR] Response | Moderate response | 8 Participants |
Secondary
Percent Change From Baseline in C-Reactive Protein (CRP)
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 43;n=3,14,5,24 | -24.02 Percent change | Standard Deviation 53.259 |
| Placebo BID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 85;n=3,14,5,22 | -43.62 Percent change | Standard Deviation 49.968 |
| Placebo TID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 85;n=3,14,5,22 | 220.05 Percent change | Standard Deviation 828.334 |
| Placebo TID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 43;n=3,14,5,24 | 63.02 Percent change | Standard Deviation 331.286 |
| GSK2982772 60 mg BID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 43;n=3,14,5,24 | -10.37 Percent change | Standard Deviation 94.318 |
| GSK2982772 60 mg BID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 85;n=3,14,5,22 | -16.42 Percent change | Standard Deviation 70.096 |
| GSK2982772 60 mg TID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 43;n=3,14,5,24 | 12.68 Percent change | Standard Deviation 107.207 |
| GSK2982772 60 mg TID | Percent Change From Baseline in C-Reactive Protein (CRP) | Day 85;n=3,14,5,22 | 274.25 Percent change | Standard Deviation 879.9 |
Secondary
Percent Change From Baseline in Interleukin 6 (IL6)
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 43;n=3,14,5,24 | 89.12 Percent change | Standard Deviation 96.649 |
| Placebo BID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 85;n=3,14,5,22 | 5.21 Percent change | Standard Deviation 16.978 |
| Placebo TID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 85;n=3,14,5,22 | 27.52 Percent change | Standard Deviation 97.215 |
| Placebo TID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 43;n=3,14,5,24 | 55.00 Percent change | Standard Deviation 257.661 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 43;n=3,14,5,24 | -3.95 Percent change | Standard Deviation 66.008 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 85;n=3,14,5,22 | -24.44 Percent change | Standard Deviation 67.817 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 43;n=3,14,5,24 | 74.49 Percent change | Standard Deviation 358.187 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Interleukin 6 (IL6) | Day 85;n=3,14,5,22 | 0.52 Percent change | Standard Deviation 106.029 |
Secondary
Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 85;n=3,11,5,17 | -34.65 Percent change | Standard Deviation 35.926 |
| Placebo BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 43;n=3,14,5,24 | -11.25 Percent change | Standard Deviation 6.591 |
| Placebo BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 85;n=3,14,5,22 | -19.77 Percent change | Standard Deviation 28.013 |
| Placebo BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 43;n=3,14,5,24 | 8.86 Percent change | Standard Deviation 27.501 |
| Placebo BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 85;n=3,14,5,22 | 32.61 Percent change | Standard Deviation 32.849 |
| Placebo BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 43;n=3,12,5,22 | -6.45 Percent change | Standard Deviation 7 |
| Placebo TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 43;n=3,12,5,22 | 32.94 Percent change | Standard Deviation 139.157 |
| Placebo TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 43;n=3,14,5,24 | 6.07 Percent change | Standard Deviation 27.883 |
| Placebo TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 85;n=3,11,5,17 | 114.18 Percent change | Standard Deviation 223.386 |
| Placebo TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 85;n=3,14,5,22 | 9.75 Percent change | Standard Deviation 41.645 |
| Placebo TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 43;n=3,14,5,24 | -4.04 Percent change | Standard Deviation 23.016 |
| Placebo TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 85;n=3,14,5,22 | 11.98 Percent change | Standard Deviation 42.337 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 43;n=3,14,5,24 | -15.36 Percent change | Standard Deviation 13.399 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 85;n=3,14,5,22 | -20.21 Percent change | Standard Deviation 19.417 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 43;n=3,14,5,24 | -26.82 Percent change | Standard Deviation 20.757 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 43;n=3,12,5,22 | -7.27 Percent change | Standard Deviation 34.373 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 85;n=3,14,5,22 | -38.26 Percent change | Standard Deviation 19.306 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 85;n=3,11,5,17 | -21.16 Percent change | Standard Deviation 31.372 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 85;n=3,14,5,22 | -2.14 Percent change | Standard Deviation 34.751 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 43;n=3,12,5,22 | -3.55 Percent change | Standard Deviation 29.506 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 43;n=3,14,5,24 | -4.07 Percent change | Standard Deviation 27.244 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-3;Day 43;n=3,14,5,24 | -4.07 Percent change | Standard Deviation 36.176 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-13;Day 85;n=3,11,5,17 | 67.91 Percent change | Standard Deviation 157.027 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Matrix Metalloproteinase-1 (MMP-1), MMP-3, and MMP-13 | MMP-1;Day 85;n=3,14,5,22 | -1.61 Percent change | Standard Deviation 28.42 |
Secondary
Percent Change From Baseline in Migration Inhibitory Factor (MIF)
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 43;n=3,14,5,24 | 8.98 Percent change | Standard Deviation 29.041 |
| Placebo BID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 85;n=3,14,5,22 | 15.39 Percent change | Standard Deviation 26.888 |
| Placebo TID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 85;n=3,14,5,22 | -15.72 Percent change | Standard Deviation 49.08 |
| Placebo TID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 43;n=3,14,5,24 | 4.69 Percent change | Standard Deviation 46.772 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 43;n=3,14,5,24 | 120.23 Percent change | Standard Deviation 362.931 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 85;n=3,14,5,22 | -11.80 Percent change | Standard Deviation 47.351 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 43;n=3,14,5,24 | 34.46 Percent change | Standard Deviation 160.4 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Migration Inhibitory Factor (MIF) | Day 85;n=3,14,5,22 | -5.76 Percent change | Standard Deviation 49.377 |
Secondary
Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1)
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 43;n=3,14,5,23 | -4.57 Percent change | Standard Deviation 19.262 |
| Placebo BID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 85;n=3,14,5,21 | -33.39 Percent change | Standard Deviation 49.411 |
| Placebo TID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 85;n=3,14,5,21 | 422.45 Percent change | Standard Deviation 514.842 |
| Placebo TID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 43;n=3,14,5,23 | 388.23 Percent change | Standard Deviation 565.617 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 43;n=3,14,5,23 | -4.37 Percent change | Standard Deviation 11.309 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 85;n=3,14,5,21 | -30.35 Percent change | Standard Deviation 36.118 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 43;n=3,14,5,23 | 156.79 Percent change | Standard Deviation 297.549 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Monocyte Chemo Attractant Protein-1 (MCP-1) | Day 85;n=3,14,5,21 | 199.94 Percent change | Standard Deviation 392.59 |
Secondary
Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14)
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 43;n=3,14,5,24 | 3.15 Percent change | Standard Deviation 47.472 |
| Placebo BID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 85;n=3,14,5,22 | 13.84 Percent change | Standard Deviation 66.492 |
| Placebo TID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 85;n=3,14,5,22 | 70.37 Percent change | Standard Deviation 199.467 |
| Placebo TID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 43;n=3,14,5,24 | 25.14 Percent change | Standard Deviation 75.189 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 43;n=3,14,5,24 | -49.21 Percent change | Standard Deviation 19.168 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 85;n=3,14,5,22 | -28.27 Percent change | Standard Deviation 17.112 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 43;n=3,14,5,24 | -22.95 Percent change | Standard Deviation 38.992 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Myeloid-related Protein 8/14 (MRP8/14) | Day 85;n=3,14,5,22 | -11.35 Percent change | Standard Deviation 77.927 |
Secondary
Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1)
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\*\[(post-dose value minus Baseline value)/ Baseline value\].
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 43;n=3,14,5,24 | -1.82 Percent change | Standard Deviation 6.578 |
| Placebo BID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 85;n=3,14,5,22 | 35.61 Percent change | Standard Deviation 73.383 |
| Placebo TID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 85;n=3,14,5,22 | -2.63 Percent change | Standard Deviation 57.144 |
| Placebo TID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 43;n=3,14,5,24 | -9.89 Percent change | Standard Deviation 37.032 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 43;n=3,14,5,24 | -7.39 Percent change | Standard Deviation 11.298 |
| GSK2982772 60 mg BID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 85;n=3,14,5,22 | 49.38 Percent change | Standard Deviation 114.161 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 43;n=3,14,5,24 | -5.59 Percent change | Standard Deviation 23.922 |
| GSK2982772 60 mg TID | Percent Change From Baseline in Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) | Day 85;n=3,14,5,22 | -1.75 Percent change | Standard Deviation 33.789 |
Secondary
Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours
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.
Time frame: Days 1, 8 and 43: 1, 2, 4 and 6 hours post-dose
Population: Pharmacokinetic GSK298772 Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;1 hour;n=5,27 | 851.000 Nanogram per milliliter | Standard Deviation 375.511 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;2 hour;n=5,27 | 656.000 Nanogram per milliliter | Standard Deviation 386.5741 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;4 hour;n=5,27 | 269.600 Nanogram per milliliter | Standard Deviation 156.3052 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;6 hour;n=5,27 | 120.240 Nanogram per milliliter | Standard Deviation 54.6881 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;1 hour;n=5,23 | 796.600 Nanogram per milliliter | Standard Deviation 397.712 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;2 hour;n=5,24 | 689.000 Nanogram per milliliter | Standard Deviation 317.5602 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;4 hour;n=5,24 | 265.000 Nanogram per milliliter | Standard Deviation 129.636 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;6 hour;n=5,23 | 112.280 Nanogram per milliliter | Standard Deviation 78.0491 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;1 hour;n=5,23 | 672.200 Nanogram per milliliter | Standard Deviation 165.447 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;2 hour;n=5,23 | 598.600 Nanogram per milliliter | Standard Deviation 253.0036 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;4 hour;n=5,23 | 313.200 Nanogram per milliliter | Standard Deviation 226.0845 |
| Placebo BID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;6 hour;n=5,23 | 177.980 Nanogram per milliliter | Standard Deviation 192.6731 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;4 hour;n=5,23 | 553.783 Nanogram per milliliter | Standard Deviation 430.5811 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;1 hour;n=5,27 | 953.037 Nanogram per milliliter | Standard Deviation 556.463 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;4 hour;n=5,24 | 520.958 Nanogram per milliliter | Standard Deviation 324.4127 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;2 hour;n=5,27 | 911.630 Nanogram per milliliter | Standard Deviation 376.7128 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;2 hour;n=5,23 | 872.652 Nanogram per milliliter | Standard Deviation 354.1155 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;4 hour;n=5,27 | 421.215 Nanogram per milliliter | Standard Deviation 211.7969 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;6 hour;n=5,23 | 444.470 Nanogram per milliliter | Standard Deviation 358.1685 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 1;6 hour;n=5,27 | 382.419 Nanogram per milliliter | Standard Deviation 485.6076 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;6 hour;n=5,23 | 332.522 Nanogram per milliliter | Standard Deviation 240.9716 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;1 hour;n=5,23 | 881.783 Nanogram per milliliter | Standard Deviation 550.4666 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 43;1 hour;n=5,23 | 862.487 Nanogram per milliliter | Standard Deviation 501.4882 |
| Placebo TID | Post-dose Plasma Concentrations of GSK2982772 on Days 1, 8, and 43 at 1, 2, 4 and 6 Hours | Day 8;2 hour;n=5,24 | 930.958 Nanogram per milliliter | Standard Deviation 446.0379 |
Secondary
Pre-dose Plasma Concentrations of GSK2982772 on Days 8 and 43
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.
Time frame: Pre-dose on Day 8 and Day 43
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Pre-dose Plasma Concentrations of GSK2982772 on Days 8 and 43 | Day 8;n=5,24 | 88.332 Nanogram per milliliter | Standard Deviation 96.5705 |
| Placebo BID | Pre-dose Plasma Concentrations of GSK2982772 on Days 8 and 43 | Day 43;n=5,23 | 33.994 Nanogram per milliliter | Standard Deviation 51.1033 |
| Placebo TID | Pre-dose Plasma Concentrations of GSK2982772 on Days 8 and 43 | Day 8;n=5,24 | 181.774 Nanogram per milliliter | Standard Deviation 322.8428 |
| Placebo TID | Pre-dose Plasma Concentrations of GSK2982772 on Days 8 and 43 | Day 43;n=5,23 | 142.792 Nanogram per milliliter | Standard Deviation 176.263 |
Secondary
Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43
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.
Time frame: Pre-dose on Days 1, 8 and 43
Population: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 1;n=3,13,5,22 | 0.450 Nanogram per milliliter | Standard Deviation 0.7794 |
| Placebo BID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 43;n=3,11,5,19 | 36.000 Nanogram per milliliter | Standard Deviation 62.3538 |
| Placebo BID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 8;n=3,12,5,17 | 1.117 Nanogram per milliliter | Standard Deviation 1.9341 |
| Placebo TID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 1;n=3,13,5,22 | 16.236 Nanogram per milliliter | Standard Deviation 56.428 |
| Placebo TID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 43;n=3,11,5,19 | 0.909 Nanogram per milliliter | Standard Deviation 2.0658 |
| Placebo TID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 8;n=3,12,5,17 | 0.509 Nanogram per milliliter | Standard Deviation 0.9879 |
| GSK2982772 60 mg BID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 8;n=3,12,5,17 | 4.640 Nanogram per milliliter | Standard Deviation 10.3754 |
| GSK2982772 60 mg BID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 1;n=3,13,5,22 | 0.546 Nanogram per milliliter | Standard Deviation 0.7909 |
| GSK2982772 60 mg BID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 43;n=3,11,5,19 | 1.512 Nanogram per milliliter | Standard Deviation 3.3809 |
| GSK2982772 60 mg TID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 1;n=3,13,5,22 | 6.309 Nanogram per milliliter | Standard Deviation 15.4993 |
| GSK2982772 60 mg TID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 43;n=3,11,5,19 | 1.445 Nanogram per milliliter | Standard Deviation 3.1606 |
| GSK2982772 60 mg TID | Pre-dose Plasma Concentrations of Methotrexate on Days 1, 8 and 43 | Day 8;n=3,12,5,17 | 11.939 Nanogram per milliliter | Standard Deviation 47.4493 |
Secondary
Trough Plasma Concentration of GSK2982772 on Day 85
Blood samples were collected to evaluate plasma concentration of GSK2982772. Pharmacokinetic parameters including trough plasma concentration was determined using standard non-compartmental methods.
Time frame: Day 85
Population: Pharmacokinetic GSK298772 Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID | Trough Plasma Concentration of GSK2982772 on Day 85 | 54.64 Nanogram per milliliter | Standard Deviation 50.714 |
| Placebo TID | Trough Plasma Concentration of GSK2982772 on Day 85 | 391.11 Nanogram per milliliter | Standard Deviation 694.27 |
Other Pre-specified
Change From Baseline in Enhancing Volume
Enhancing volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.
Other Pre-specified
Change From Baseline in Joint Volume
Joint volume was planned to be measured by DCE-MRI in most affected hand/wrist at indicated time points.
Time frame: Baseline (Day 1 pre-dose), Days 43 and 85
Population: Safety Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.