NCT01597635

The Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury

A Two Part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586881 in Patients With Acute Lung Injury

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is an early phase (phase IIa), randomized, multi-center study in subjects with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The purpose of this study is to investigate the safety of GSK2586881 and to determine what effects it has on people with Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). The study has two parts: Part A will be an open-label investigation in five subjects. Part B will be a double-blind, placebo controlled investigation and will involve approximately 60 subjects.

Detailed description

The acute respiratory distress syndrome (ARDS) is a form of severe acute 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, tolerability and pharmacodynamics of GSK2586881, a recombinant human angiotensin converting enzyme type 2 (rhACE2). ACE2 is involved in the Renin-Angiotensin System (RAS), which controls blood pressure, electrolytes and intravascular fluid volume. A key function of rhACE2 is believed to be the cleavage of Angiotensin II (Ang II) to Ang (1-7), which have opposing physiological roles. Elevated levels of Ang II are associated with vasoconstriction, inflammation, fibrosis, vascular leak, and sodium absorption. Ang (1-7) appears to be a counterregulatory protein in the RAS; associated with vasodilation, anti-proliferation, antiinflammation, and reduced vascular leak. It has been observed that levels of Ang II are increased in humans with ALI/ ARDS. It is expected that the reduction of Ang II should have a positive impact on ALI and ARDS.

Conditions

• Lung Injury, Acute

Interventions

Type	Name	Description
DRUG	Dose 1 GSK2586881	Low dose GSK2586881 administered intravenously
DRUG	Dose 2 GSK2586881	Medium dose GSK2586881 administered intravenously
DRUG	Dose 3 GSK2586881	Medium-High dose GSK2586881 administered intravenously
DRUG	Dose 4 GSK2586881	High dose GSK2586881 administered intravenously
DRUG	Placebo (saline)	Administered intravenously to match intervention

Timeline

• Start date: 2012-09-01
• Primary completion: 2014-10-01
• Completion: 2014-10-06
• First posted: 2012-05-14
• Last updated: 2017-09-28
• Results posted: 2017-09-28

Locations

19 sites across 2 countries: United States, Canada