Clinical trial NCT00996840
Conditions: Lung Injury, Acute
Keywords: dilmapimod p38 SB-681323 Acute Lung Injury (ALI) Acute Respiratory Distress Syndrome (ARDS)
Sponsor: GlaxoSmithKline
Start date: 2009-10-16; Completion date: 2013-02-09
Enrollment: 77 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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.

Arms: arm 1: 3mg SB-681323 Intravenous administration, infused over 4 hours arm 2: 7.5 mg SB-681323 Intravenous administration infused over 24 hours arm 3: 7.5 mg SB-681323 Intravenous administration infused over 4 hours arm 4: 10 mg SB-681323 Intravenous administration infused over 24 hours arm 5: Placebo to match intervention
Interventions: intervention 1: SB-681323 Intravenous 3mg intervention 2: SB-681323 Intravenous 7.5 mg intervention 3: SB-681323 Intravenous 7.5mg intervention 4: SB-681323 Intravenous 10mg intervention 5: Placebo
Intervention descriptions: intervention 1: 3 mg SB-681323 Intravenous administration infused over 4 hours intervention 2: 7.5 mg SB-681323 Intravenous administration infused over 24 hours intervention 3: 7.5 mg SB-681323 Intravenous administration infused over 4 hours intervention 4: 10 mg SB-681323 Intravenous administration infused over 24 hours intervention 5: Placebo to match intervention

Protocol documents: