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SB-681323

Phase 2

Arthritis, Rheumatoid | Small molecule | Immunology |GSK plc|Last Updated: Oct 18, 2017

Success Probability

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Trial Design

RandomizedDouble-BlindUNCONTROLLEDDMC
Total Trials4
Total Enrollment189

FDA Designations

No designations recorded

Clinical trial landscape

SB-681323 · 6 trials · 4 indications

Phase 2 4Phase 1 2
NCT00996840SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDSLung Injury, Acute
COMPLETED77 Analytics
NCT00291902A Pharmacokinetic Study Of SB-681323 In Subjects With Coronary Heart Disease Undergoing Percutaneous InterventionCoronary Heart Disease
COMPLETED80 Analytics
NCT00320450SB-681323 In Subjects With Rheumatoid ArthritisArthritis, Rheumatoid
COMPLETED78 Analytics
NCT00134693A Single Dose Of Compound SB-681323 Compared To Prednisolone On A Protein That Is an Indicator For Rheumatoid ArthritisArthritis, Rheumatoid
COMPLETED77 Analytics
PHASE2COMPLETED
SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDS
Lung Injury, AcuteUnlock trial analytics
PHASE2COMPLETED
A Pharmacokinetic Study Of SB-681323 In Subjects With Coronary Heart Disease Undergoing Percutaneous Intervention
Coronary Heart DiseaseUnlock trial analytics
PHASE2COMPLETED
SB-681323 In Subjects With Rheumatoid Arthritis
Arthritis, RheumatoidUnlock trial analytics
PHASE2COMPLETED
A Single Dose Of Compound SB-681323 Compared To Prednisolone On A Protein That Is an Indicator For Rheumatoid Arthritis
Arthritis, RheumatoidUnlock trial analytics

Study Endpoints

Primary Endpoints

Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Mean hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, white blood cell count were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Hematology Parameters- Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Mean hematology parameters including hemoglobin, MCHC were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Hematology Parameters- Mean Corpuscle Hemoglobin
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Hematology parameter mean corpuscle hemoglobin was reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Hematology Parameters-Mean Corpuscle Volume
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Absolute values of mean corpuscle volume were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Hematology Parameters-reticulocytes, Red Blood Cell Count
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Absolute values of reticulocytes and red blood cell count were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Clinical Chemistry Parameters- Albumin and Total Protein
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Absolute values of albumin and total protein were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Clinical Chemistry Parameters-alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Absolute values of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and gamma glutamyl transferase were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Clinical Chemistry Parameters- Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Absolute values of direct bilirubin, total bilirubin, creatinine and uric acid were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Clinical Chemistry Parameters- Calcium, Chloride, Glucose, Bicarbonate, Potassium, Sodium and Ratio of Urea to Blood Urea Nitrogen (Urea/BUN)
"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Absolute values of calcium, chloride, glucose, bicarbonate, potassium, sodium and Urea/BUN were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Clinical Chemistry Parameters-estradiol
Day 1 (pre-dose) and Day 3 (24 h)

Absolute values of Estradiol were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.

Mean Clinical Chemistry Parameters-Blood pH at Screening
Screening

Absolute values of Blood pH at screening were reported as clinical chemistry parameter.

Vital Parameter- Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"

Absolute values of SBP and DBP were reported.

Vital Parameter: Mean Heart Rate
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"

Absolute values of mean heart rate were reported.

Vital Sign: Mean Percent Oxygen (O2) in Blood
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"

Absolute values of mean percent O2 in blood were reported.

Vital Signs: Mean Oxygen Saturation (SaO2) Via Pulse Oximetry
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Assessment of SaO2 via pulse oximetry was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.

Vital Signs: Mean Level of Positive End Expiratory Pressure
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Assessment of level of positive end expiratory pressure was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.

Vital Signs: Mean Level of Peak and Plateau Ventilator Pressures
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Assessment of mean level of peak and plateau ventilator pressures was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.

Vital Signs: Mean Oxygen Requirement (FiO2) Via Pulse Oximetry
For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Assessment of mean FiO2 via pulse oximetry was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.

Mean Electrocardiogram (ECG) Parameters Including PR, QRS, QT, and QTcB, QTcF, RR Intervals
Day 2, pre-dose, Day 3, pre-dose, Day 3, 24 h and Follow-up (Day 7)

12-lead ECGs were obtained at each timepoint during the study using an ECG machine that automatically calculated the heart rate and measures RR, PR, QRS, QT, and QTc intervals. Absolute mean values of PR, QRS, QT, and QTcB, QTcF, RR intervals were reported.

Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
Up to Follow-up (Day 7)

AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Patient safety Tolerability Anti-inflammatory effect (high sensitivity C-reactive Protein)
28 days
Serum levels of CRP at the end of study (after 28 days of treatment) following repeat dosing with SB-681323 (7.5mg/day) compared with placebo.
28 Days
Analysis for C-Reactive protein (CRP) levels 72 hours post-dose following SB-681323
Day 3 (at 72 hour)

CRP levels were compared between SB-681323 and placebo 72 hours post-dose. The ratio of the dose response relationship of placebo and 7.5mg, 15mg and 25mg of SB-681323 has been presented.

Safety of SB-681323 in terms of frequency/ nature of adverse events and changes in ECG patterns, vital signs and clinical laboratory parameters (including liver function tests) seen upto 48h after a single intravenous dose.
The primary outcome measure is the values of liver function tests following dosing with methotrexate alone (Day 1) and methotrexate and SB-681323 or placebo (Day 15).

Secondary Endpoints

Mean Serum Interleukin-6 Levels
6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Serum CXCL8 (Interleuin-8) Levels
6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Serum C-Reactive Protein (CRP) Levels
6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort 1 - SB-681323 Intravenous 3mgEXPERIMENTAL3mg SB-681323 Intravenous administration, infused over 4 hours
Cohort 2 - SB-681323 Intravenous 7.5 mgEXPERIMENTAL7.5 mg SB-681323 Intravenous administration infused over 24 hours
Cohort 3 - SB-681323 Intravenous 7.5mgEXPERIMENTAL7.5 mg SB-681323 Intravenous administration infused over 4 hours
Cohort 4 - SB-681323 Intravenous 10mgEXPERIMENTAL10 mg SB-681323 Intravenous administration infused over 24 hours
Combined PlaceboEXPERIMENTALPlacebo to match intervention

Interventions

NameTypeDescription
SB-681323 Intravenous 3mgDRUG3 mg SB-681323 Intravenous administration infused over 4 hours
SB-681323 Intravenous 7.5 mgDRUG7.5 mg SB-681323 Intravenous administration infused over 24 hours
SB-681323 Intravenous 7.5mgDRUG7.5 mg SB-681323 Intravenous administration infused over 4 hours
SB-681323 Intravenous 10mgDRUG10 mg SB-681323 Intravenous administration infused over 24 hours
PlaceboOTHERPlacebo to match intervention
SB-681323DRUG -
PrednisoloneDRUG -
SB-681323 oral tabletsDRUG -
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites6

Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Male or female, 18 - 80 years of age (inclusive) with major trauma admitted to the Intensive Care Unit (ICU). * Injury Severity score (ISS) \>16 to \<70 (exclusive) * A female ...

Countries:United StatesDenmarkPolandGermanyHong KongItalyNorwaySpainSwedenUnited KingdomAustraliaFranceRussia
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Frequently asked questions about SB-681323

What is SB-681323 used for?

SB-681323 is an investigational small molecule being studied for several conditions, including acute lung injury, rheumatoid arthritis, coronary heart disease, chronic obstructive pulmonary disease (COPD), and neuropathic pain. It is in Phase 2 clinical development for these indications.

What does SB-681323 target?

SB-681323 is a small molecule being developed for inflammatory and pain conditions. Its specific molecular target has not been disclosed in available information, so its exact mechanism of action is not described here.

Who makes SB-681323?

SB-681323 is being developed by GSK plc, a global biopharma company listed on the stock exchange under the ticker GSK. GSK is conducting clinical trials to evaluate the drug's safety and efficacy.

What phase is SB-681323 in?

SB-681323 is in Phase 2 clinical development. It has completed four clinical trials, including Phase 2 studies in COPD, coronary heart disease, and acute lung injury, as well as a Phase 1 study in COPD. It is not yet approved by regulatory authorities.

What clinical trials is SB-681323 in?

SB-681323 has completed four clinical trials: NCT00144859 in COPD patients, NCT00291902 in coronary heart disease patients undergoing percutaneous intervention, NCT00380133 in COPD patients, and NCT00996840 in patients at risk of acute lung injury or ARDS. All trials are completed.

Is SB-681323 the same as SB681323?

Yes, SB-681323 is also referred to as SB681323 in some clinical trial records. Both names refer to the same investigational drug being developed by GSK plc for inflammatory and pain-related conditions.