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

• Status: Completed
• Trial end date: 2013-02-09
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

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 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.

• 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.

Exclusion Criteria:

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).

• 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.