Lung Injury, AcutePhase 2NCT00996840

SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDS

A Phase 2 study testing SB-681323 Intravenous 3mg, SB-681323 Intravenous 7.5 mg and SB-681323 Intravenous 7.5mg in people with Lung Injury, Acute, run by GlaxoSmithKline at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Lung Injury, Acute
What is being tested?: SB-681323 Intravenous 3mg, SB-681323 Intravenous 7.5 mg and SB-681323 Intravenous 7.5mg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 77 participants
Where: 6 sitesUnited States
Study dates: 16 Oct 2009to 9 Feb 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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 subject is eligible to participate if she is of non-child-bearing potential or of:
Child-bearing potential and agrees to use one of the approved contraception methods (oral contraceptive, either combined or progesterone alone, injectable progesterone, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device (IUD) or intrauterine system (IUS) with less than 1% non-effectiveness, documented male partner sterilization, double barrier method, i.e. condom and occlusive cap plus spermicidal agent) for an appropriate period of time (as determined by the product label or investigator, if applicable. Female subjects must agree to use contraception until one week post-last dose, if applicable.
Male subjects must agree to use one of the approved contraception methods (abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject, condom during non-vaginal intercourse with any partner (male or female), condom and occlusive cap plus spermicidal agent during sexual intercourse with a female) if applicable. This criterion must be followed from the time of the first dose of study medication until one week post-last dose, if applicable.

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BMI within the range 19.0 - 35.0 kg/m2 inclusive (clinical estimate of height and weight is acceptable).
The subject or legal decision maker is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
The subject must be randomized into the study within 24-26 hours from the time of trauma.

Who cannot join

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Known positive Hepatitis B surface antigen or Hepatitis C antibody.
Known positive test for HIV antibody.
A known history of substance abuse, alcohol abuse, or regular alcohol consumption within 6 months of the study defined as:
an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

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History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
Haemoglobin < 7g/dL.
Pregnant females as determined by positive serum or urine hCG test prior to dosing.
Lactating females.
Unwillingness or inability to follow the procedures outlined in the protocol.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Diagnosis of ALI at admission.
Head trauma (Abbreviated Injury Score [AIS]>3), liver trauma (AIS>2), or trauma that in the opinion of the Principle Investigator or GSK medical monitor is deemed unsurvivable.
Known history of neuromuscular disease or cord injury at C5 or above.
Elevated ALT or AST > 1.5 ULN.
History of bone marrow or solid organ transplant.
Known history of auto-immune disorder in which immunosuppressive agents, other than prednisone, were required within the last 6 weeks.
Known to be receiving oral or intravenous corticosteroids within 7 days of admission.
Subject with active tuberculosis or being treated for active tuberculosis.
Known history of malignancy within the past 5 years with the exception of successfully treated squamous cell or basal cell cancer of the skin.
Arterial blood pH less than 7.1 or serum HCO3 - <15 before infusion is started.
Persistent cardiovascular instability requiring therapy with more than one vasopressor.
A patient will be excluded if in the judgement of the Principle Investigator or GSK medical monitor their participation could jeopardize the health of the subject or the integrity of the study.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

GSK Investigational Site
Durham, North Carolina, 27710
GSK Investigational Site
Lexington, Kentucky, 40536-0293
GSK Investigational Site
Nashville, Tennessee, 37232-7110
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213
GSK Investigational Site
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Assessment of the Anti-Inflammatory Activity, Efficacy and Safety of Intravenous SB-681323 in Subjects at Risk for Development of Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS).

This is an early phase (Phase IIa), randomized, double-blind, parallel group, multi-centre study for subjects with trauma (physical injury) who are at risk for developing Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). The primary purpose of the study is to evaluate the safety and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha (MAPK) (prevents inflammation of tissue), in comparison to a placebo.

Read the detailed description

The acute respiratory distress syndrome (ARDS) is a form of severe lung injury (ALI) characterized by hypoxemic respiratory failure (the lungs are unable to absorb oxygen to the arterial blood) and non-cardiogenic pulmonary edema (accumulation of fluid in the lungs). The syndrome may be caused by direct or indirect injury to the lungs. It is associated with a mortality rate of up to 40-50%. There are no marketed pharmacologic therapies for this devastating syndrome.

This study aims to assess the safety and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha mitogen-activated protein kinase.

The rationale behind the development of this drug is that there are elevated levels of circulating pro-inflammatory agents, such as cytokines which are biological agents that increase levels of inflammation in the lungs. These agents are part of an 'inflammatory loop' and it may be beneficial to the condition to dampen this loop.

p38 mitogen activated protein kinase (MAPK) plays a major role in the regulation and activation of intracellular proteins which are subsequently involved in the regulation of the cytokines. The pathway is activated by 'stress', such as injury, causing the inflammation. Therefore, 'dampening' this system should reduce the level of inflammation.

This study will investigate the anti-inflammatory activity, efficacy (effectiveness at achieving the desired effect) and safety of SB-681323.

To measure the efficacy of the drug, biomarkers will be measured. Biomarkers are biological agents in the body that are effected by the presence of specific injury or inflammation and are directly or indirectly linked to a regulatory system of event in the body. They are used to measure for the presence and severity of the condition in question. This study will investigate biomarkers linked directly or indirectly to the p38 alpha regulatory mechanism/system. We will be measuring biomarkers such as serum inflammatory biomarkers, coagulation (blood clotting) system biomarkers, biomarkers of endothelial cell / neutrophil interaction and biomarkers of lung epithelial cell injury.

Conditions: Lung Injury, Acute
Being tested: SB-681323 Intravenous 3mg, SB-681323 Intravenous 7.5 mg, SB-681323 Intravenous 7.5mg, SB-681323 Intravenous 10mg, Placebo
Keywords: dilmapimod, p38, SB-681323, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS)
Medical subject headings: Acute Lung Injury, Respiratory Distress Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SB-681323 Intravenous 3mgDrug
3 mg SB-681323 Intravenous administration infused over 4 hours
SB-681323 Intravenous 7.5 mgDrug
7.5 mg SB-681323 Intravenous administration infused over 24 hours
SB-681323 Intravenous 7.5mgDrug
7.5 mg SB-681323 Intravenous administration infused over 4 hours
SB-681323 Intravenous 10mgDrug
10 mg SB-681323 Intravenous administration infused over 24 hours
PlaceboOther
Placebo to match intervention

Study groups in NCT00996840
Study group	Role	What they receive
Cohort 1 - SB-681323 Intravenous 3mg	Experimental	3mg SB-681323 Intravenous administration, infused over 4 hours Receives: Drug: SB-681323 Intravenous 3mg
Cohort 2 - SB-681323 Intravenous 7.5 mg	Experimental	7.5 mg SB-681323 Intravenous administration infused over 24 hours Receives: Drug: SB-681323 Intravenous 7.5 mg
Cohort 3 - SB-681323 Intravenous 7.5mg	Experimental	7.5 mg SB-681323 Intravenous administration infused over 4 hours Receives: Drug: SB-681323 Intravenous 7.5mg
Cohort 4 - SB-681323 Intravenous 10mg	Experimental	10 mg SB-681323 Intravenous administration infused over 24 hours Receives: Drug: SB-681323 Intravenous 10mg
Combined Placebo	Experimental	Placebo to match intervention Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Hematology Parameters- Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Hematology Parameters- Mean Corpuscle Hemoglobin
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Hematology Parameters-Mean Corpuscle Volume
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Hematology Parameters-reticulocytes, Red Blood Cell Count
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Clinical Chemistry Parameters- Albumin and Total Protein
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Clinical Chemistry Parameters-alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Clinical Chemistry Parameters- Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Clinical Chemistry Parameters- Calcium, Chloride, Glucose, Bicarbonate, Potassium, Sodium and Ratio of Urea to Blood Urea Nitrogen (Urea/BUN)
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.
Measured: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"
Mean Clinical Chemistry Parameters-estradiol
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.
Measured: Day 1 (pre-dose) and Day 3 (24 h)
Mean Clinical Chemistry Parameters-Blood pH at Screening
Absolute values of Blood pH at screening were reported as clinical chemistry parameter.
Measured: Screening
Vital Parameter- Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Absolute values of SBP and DBP were reported.
Measured: 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)"
Vital Parameter: Mean Heart Rate
Absolute values of mean heart rate were reported.
Measured: 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)"
Vital Sign: Mean Percent Oxygen (O2) in Blood
Absolute values of mean percent O2 in blood were reported.
Measured: 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)"
Vital Signs: Mean Oxygen Saturation (SaO2) Via Pulse Oximetry
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.
Measured: 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"
Vital Signs: Mean Level of Positive End Expiratory Pressure
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.
Measured: 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"
Vital Signs: Mean Level of Peak and Plateau Ventilator Pressures
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.
Measured: 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"
Vital Signs: Mean Oxygen Requirement (FiO2) Via Pulse Oximetry
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.
Measured: 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"
Mean Electrocardiogram (ECG) Parameters Including PR, QRS, QT, and QTcB, QTcF, RR Intervals
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.
Measured: Day 2, pre-dose, Day 3, pre-dose, Day 3, 24 h and Follow-up (Day 7)
Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
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.
Measured: Up to Follow-up (Day 7)

Secondary outcomes (8)

Mean Serum Interleukin-6 Levels
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of Serum interleukin-6 levels at these specified time oints were reported.
Measured: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Serum CXCL8 (Interleuin-8) Levels
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of Serum CXCL8 (Interleuin-8) levels at these specified time points were reported.
Measured: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Serum C-Reactive Protein (CRP) Levels
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of serum CRP levels at these specified time points were reported.
Measured: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I
Samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of soluble tumor necrosis factor receptors-I levels at these specified time points were reported.
Measured: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of MPO levels at these specified time points were reported.
Measured: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24)
Absolute values of the mean AUC 0-24 of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h10minutes [min], 24h45min, 27, 34, 40, 80 h since doing on Day 3).
Measured: For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose)
Mean Average Concentration (Cavg) of SB-681323
Absolute values of mean Cavg of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3).
Measured: For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10minutes [min], 24h 45min, 27, 34, 40, 80 h since doing on Day 3)
Maximum Observed Concentration (Cmax) of SB-681323
Absolute values of the Cmax of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3).
Measured: For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Oct 20099 Feb 2013

First posted16 Oct 2009 (estimated)
Study start16 Oct 2009
Primary completion9 Feb 2013
Study completion9 Feb 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Lung Injury, AcuteStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00996840
Sponsor's protocol ID: 111592
Status last verified: Sep 2017
First submitted: 15 Oct 2009
Last updated: 18 Oct 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

Christie JD, Vaslef S, Chang PK, May AK, Gunn SR, Yang S, Hardes K, Kahl L, Powley WM, Lipson DA, Bayliffe AI, Lazaar AL. A Randomized Dose-Escalation Study of the Safety and Anti-Inflammatory Activity of the p38 Mitogen-Activated Protein Kinase Inhibitor Dilmapimod in Severe Trauma Subjects at Risk for Acute Respiratory Distress Syndrome. Crit Care Med. 2015 Sep;43(9):1859-69. doi: 10.1097/CCM.0000000000001132.
PubMed 26102252

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of the Anti-Inflammatory Activity, Efficacy and Safety of Intravenous SB-681323 in Subjects at Risk for Development of Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS).
ClinicalTrials.gov ID: NCT00996840
Acronym / sponsor ID: 111592
Conditions: Lung Injury, Acute
Keywords: dilmapimod, p38, SB-681323, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 77 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 16 Oct 2009 (actual)
Primary completion: 9 Feb 2013 (actual)
Study completion: 9 Feb 2013 (actual)
First posted: 16 Oct 2009 (estimated)
Results: Posted 18 Oct 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This study aims to assess the safety and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha mitogen-activated protein kinase.

This study will investigate the anti-inflammatory activity, efficacy (effectiveness at achieving the desired effect) and safety of SB-681323.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 5

Arm	Type	Receives
Cohort 1 - SB-681323 Intravenous 3mg	Experimental	Drug: SB-681323 Intravenous 3mg3mg SB-681323 Intravenous administration, infused over 4 hours
Cohort 2 - SB-681323 Intravenous 7.5 mg	Experimental	Drug: SB-681323 Intravenous 7.5 mg7.5 mg SB-681323 Intravenous administration infused over 24 hours
Cohort 3 - SB-681323 Intravenous 7.5mg	Experimental	Drug: SB-681323 Intravenous 7.5mg7.5 mg SB-681323 Intravenous administration infused over 4 hours
Cohort 4 - SB-681323 Intravenous 10mg	Experimental	Drug: SB-681323 Intravenous 10mg10 mg SB-681323 Intravenous administration infused over 24 hours
Combined Placebo	Experimental	Other: PlaceboPlacebo to match intervention

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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 subject is eligible to participate if she is of non-child-bearing potential or of:
Child-bearing potential and agrees to use one of the approved contraception methods (oral contraceptive, either combined or progesterone alone, injectable progesterone, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device (IUD) or intrauterine system (IUS) with less than 1% non-effectiveness, documented male partner sterilization, double barrier method, i.e. condom and occlusive cap plus spermicidal agent) for an appropriate period of time (as determined by the product label or investigator, if applicable. Female subjects must agree to use contraception until one week post-last dose, if applicable.

Key exclusion criteria (24 listed)

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Known positive Hepatitis B surface antigen or Hepatitis C antibody.
Known positive test for HIV antibody.
A known history of substance abuse, alcohol abuse, or regular alcohol consumption within 6 months of the study defined as:
an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SB-681323 Intravenous 3mg3 mg SB-681323 Intravenous administration infused over 4 hours	Drug	Cohort 1 - SB-681323 Intravenous 3mg
SB-681323 Intravenous 7.5 mg7.5 mg SB-681323 Intravenous administration infused over 24 hours	Drug	Cohort 2 - SB-681323 Intravenous 7.5 mg
SB-681323 Intravenous 7.5mg7.5 mg SB-681323 Intravenous administration infused over 4 hours	Drug	Cohort 3 - SB-681323 Intravenous 7.5mg
SB-681323 Intravenous 10mg10 mg SB-681323 Intravenous administration infused over 24 hours	Drug	Cohort 4 - SB-681323 Intravenous 10mg
PlaceboPlacebo to match intervention	Other	Combined Placebo

Primary outcome

Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count
Time frame: "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)
Time frame: "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
Time frame: "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
Time frame: "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
Time frame: "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
Time frame: "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
Time frame: "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
Time frame: "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)
Time frame: "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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.

8 secondary outcomes

Mean Serum Interleukin-6 Levels
Time frame: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Serum CXCL8 (Interleuin-8) Levels
Time frame: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Serum C-Reactive Protein (CRP) Levels
Time frame: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I
Time frame: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels
Time frame: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1
Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24)
Time frame: For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose)
Mean Average Concentration (Cavg) of SB-681323
Time frame: For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10minutes [min], 24h 45min, 27, 34, 40, 80 h since doing on Day 3)
Maximum Observed Concentration (Cmax) of SB-681323
Time frame: For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3)

Results and safety

Results posted to the registry on 18 Oct 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Combined Placebo	20	19
Cohort 1-SB-681323, 3 mg, 4 h	9	7
Cohort 2-SB-681323, 7.5 mg, 24 h	12	11
Cohort 3-SB-681323, 7.5 mg, 4 h	18	17
Cohort 4-SB-681323, 10 mg, 24 h	18	16

Primary outcome: Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count

Time frame: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)". Mean (Standard Deviation). Unit: Giga cells per liter

Measure	Combined Placebo n = 20	Cohort 1-SB-681323, 3 mg, 4 h n = 9	Cohort 2-SB-681323, 7.5 mg, 24 h n = 12	Cohort 3-SB-681323, 7.5 mg, 4 h n = 18	Cohort 4-SB-681323, 10 mg, 24 h n = 18
Basophils: Day 2, pre-dose	0.0305 (0.04196)	0.0163 (0.01188)	0.0208 (0.02843)	0.0153 (0.01125)	0.0258 (0.02134)
Basophils: Day 3, pre-dose	0.0291 (0.03036)	0.0129 (0.00756)	0.0209 (0.02737)	0.0176 (0.01562)	0.0279 (0.03191)
Basophils: Day 3, 24 h	0.0239 (0.02062)	0.0294 (0.02809)	0.0300 (0.02374)	0.0284 (0.02762)	0.0315 (0.04240)
Basophils: Follow up (Day 7)	0.0389 (0.03660)	0.0314 (0.02340)	0.0300 (0.02625)	0.0345 (0.03965)	0.0240 (0.02501)
Eosinophils: Day 2, pre-dose	0.0968 (0.18817)	0.0676 (0.07149)	0.0633 (0.07451)	0.0331 (0.04319)	0.0724 (0.07411)
Eosinophils: Day 3, pre-dose	0.1588 (0.18027)	0.0894 (0.06882)	0.0964 (0.10112)	0.0746 (0.06376)	0.0664 (0.04955)
Eosinophils: Day 3, 24 h	0.2544 (0.18852)	0.1538 (0.07558)	0.1400 (0.14365)	0.1345 (0.12560)	0.1142 (0.07005)
Eosinophils: Follow up (Day 7)	0.3713 (0.29748)	0.2866 (0.25120)	0.1900 (0.16445)	0.2390 (0.08483)	0.1998 (0.14855)

Population analysed: All subject Population comprised of as all participant who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.

Primary outcome: Mean Hematology Parameters- Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)

Time frame: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)". Mean (Standard Deviation). Unit: Grams per liter (g/L)

Measure	Combined Placebo n = 20	Cohort 1-SB-681323, 3 mg, 4 h n = 9	Cohort 2-SB-681323, 7.5 mg, 24 h n = 12	Cohort 3-SB-681323, 7.5 mg, 4 h n = 18	Cohort 4-SB-681323, 10 mg, 24 h n = 18
Hemoglobin : Day 2, pre-dose	100.8 (17.05)	97.0 (16.27)	97.8 (22.04)	88.4 (12.46)	97.2 (20.40)
Hemoglobin : Day 3, pre-dose	90.6 (15.27)	96.0 (17.48)	93.7 (19.40)	82.9 (9.29)	95.2 (20.85)
Hemoglobin : Day 3, 24 h	91.9 (12.94)	96.5 (16.50)	93.0 (15.36)	84.7 (9.73)	95.1 (19.37)
Hemoglobin: follow up (Day 7)	94.1 (14.97)	103.5 (16.42)	99.6 (15.49)	88.8 (8.93)	99.2 (16.36)
MCHC :Day 2, pre-dose	341.2 (10.96)	343.8 (4.17)	339.3 (6.96)	339.1 (9.43)	343.6 (10.63)
MCHC : Day 3, pre-dose	337.4 (9.30)	343.1 (8.15)	338.7 (7.64)	339.1 (7.43)	341.2 (8.73)
MCHC : Day 3, 24 h	338.2 (9.33)	342.9 (6.90)	338.1 (9.34)	336.4 (10.03)	342.8 (9.60)
MCHC : Follow up (Day 7)	333.4 (12.09)	339.5 (10.74)	337.8 (9.72)	331.1 (11.89)	342.5 (9.28)

Population analysed: All subject population. Only those participants available at the specified time points were analyzed.

Primary outcome: Mean Hematology Parameters- Mean Corpuscle Hemoglobin

Time frame: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)". Mean (Standard Deviation). Unit: Picogram (pg)

Measure	Combined Placebo n = 20	Cohort 1-SB-681323, 3 mg, 4 h n = 9	Cohort 2-SB-681323, 7.5 mg, 24 h n = 12	Cohort 3-SB-681323, 7.5 mg, 4 h n = 18	Cohort 4-SB-681323, 10 mg, 24 h n = 18
Mean Corpuscle Hemoglobin: Day 2, pre-dose	30.46 (1.340)	30.74 (1.241)	30.11 (1.262)	30.18 (1.997)	31.10 (1.160)
Mean Corpuscle Hemoglobin: Day 3, pre-dose	30.21 (1.319)	30.78 (1.290)	30.22 (1.135)	30.19 (1.771)	30.77 (1.332)
Mean Corpuscle Hemoglobin: Day 3, 24 h	30.25 (1.359)	30.80 (1.153)	30.33 (1.378)	30.06 (1.808)	30.92 (1.274)
Mean Corpuscle Hemoglobin:Follow up (Day 7)	30.02 (1.141)	30.64 (1.308)	30.13 (1.234)	29.82 (1.768)	31.08 (1.415)

Population analysed: All subject population. Only those participants available at the specified time points were analyzed.

Primary outcome: Hematology Parameters-Mean Corpuscle Volume

Time frame: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)". Mean (Standard Deviation). Unit: Femtoliter

Measure	Combined Placebo n = 20	Cohort 1-SB-681323, 3 mg, 4 h n = 9	Cohort 2-SB-681323, 7.5 mg, 24 h n = 12	Cohort 3-SB-681323, 7.5 mg, 4 h n = 18	Cohort 4-SB-681323, 10 mg, 24 h n = 18
Mean Corpuscle Volume:Day 2, pre-dose	89.30 (4.024)	89.59 (3.379)	88.33 (3.367)	89.15 (4.828)	90.63 (2.809)
Mean Corpuscle Volume: Day 3, pre-dose	89.85 (3.833)	89.70 (2.804)	89.00 (3.742)	89.18 (4.375)	90.48 (3.075)
Mean Corpuscle Volume: Day 3, 24 h	89.41 (3.920)	89.96 (2.295)	89.50 (3.920)	89.45 (4.285)	90.08 (2.510)
Mean Corpuscle Volume: Follow up (Day 7)	90.12 (3.430)	89.86 (2.738)	89.67 (3.869)	90.43 (4.079)	90.75 (3.115)

Population analysed: All subject population. Only those participants available at the specified time points were analyzed.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to follow up period (Day 7).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Combined Placebo	1 of 20 (5%)	18 of 20 (90%)	0 of 20
Cohort 1-SB-681323, 3 mg, 4 h	1 of 9 (11.1%)	7 of 9 (77.8%)	0 of 9
Cohort 2-SB-681323, 7.5 mg, 24 h	1 of 12 (8.3%)	10 of 12 (83.3%)	0 of 12
Cohort 3-SB-681323, 7.5 mg, 4 h	4 of 18 (22.2%)	16 of 18 (88.9%)	0 of 18
Cohort 4-SB-681323, 10 mg, 24 h	0 of 18 (0%)	14 of 18 (77.8%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26102252Christie JD, Vaslef S, Chang PK, May AK, Gunn SR, Yang S, Hardes K, Kahl L, Powley WM, Lipson DA, Bayliffe AI, Lazaar AL. A Randomized Dose-Escalation Study of the Safety and Anti-Inflammatory Activity of the p38 Mitogen-Activated Protein Kinase Inhibitor Dilmapimod in Severe Trauma Subjects at Risk for Acute Respiratory Distress Syndrome. Crit Care Med. 2015 Sep;43(9):1859-69. doi: 10.1097/CCM.0000000000001132.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SB-681323 Intravenous 3mg, SB-681323 Intravenous 7.5 mg and SB-681323 Intravenous 7.5mg in people with Lung Injury, Acute, run by GlaxoSmithKline at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count (time frame: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00996840, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2017.