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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01597635
First Posted: May 14, 2012
Last Update Posted: September 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
Results First Submitted: July 23, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition: Lung Injury, Acute
Interventions: Drug: Dose 1 GSK2586881
Drug: Dose 2 GSK2586881
Drug: Dose 3 GSK2586881
Drug: Dose 4 GSK2586881
Drug: Placebo (saline)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted across 5 centers in United States and 5 centers in Canada from 20 September 2012 to 06 October 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 46 participants were randomized for this study of which 44 participants (5 participants in Part A and 39 participants in Part B) received at least one dose of study medication.

Reporting Groups
  Description
Part A Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kilograms [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Part B (Placebo BID) Eligible participants received intravenous matching placebo (saline solution) twice daily (BID) as a slow infusion over 3-5 minutes for 3 days.
Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.

Participant Flow for 2 periods

Period 1:   Part A
    Part A   Part B (Placebo BID)   Part B (GSK2586881 BID)
STARTED   5   0   0 
COMPLETED   2   0   0 
NOT COMPLETED   3   0   0 
Adverse Event                3                0                0 

Period 2:   Part B
    Part A   Part B (Placebo BID)   Part B (GSK2586881 BID)
STARTED   0   20   19 
COMPLETED   0   14   15 
NOT COMPLETED   0   6   4 
Adverse Event                0                0                1 
Protocol Violation                0                1                0 
Protocol-defined stopping criteria                0                4                3 
Withdrawal by Subject                0                1                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Part A Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Part B (Placebo BID) Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Total Total of all reporting groups

Baseline Measures
   Part A   Part B (Placebo BID)   Part B (GSK2586881 BID)   Total 
Overall Participants Analyzed 
[Units: Participants]
 5   20   19   44 
Age, Customized 
[Units: Participants]
Count of Participants
       
18-80 years   5   20   19   44 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      2  40.0%      7  35.0%      6  31.6%      15  34.1% 
Male      3  60.0%      13  65.0%      13  68.4%      29  65.9% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
       
American Indian or Alaska Native      0   0.0%      1   5.0%      0   0.0%      1   2.3% 
Asian      0   0.0%      1   5.0%      1   5.3%      2   4.5% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      0   0.0%      1   5.0%      0   0.0%      1   2.3% 
White      5 100.0%      17  85.0%      18  94.7%      40  90.9% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Heart Rate Assessments Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

2.  Primary:   Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

3.  Primary:   Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

4.  Primary:   Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

5.  Primary:   Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

6.  Primary:   Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

7.  Primary:   Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

8.  Primary:   Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

9.  Primary:   Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

10.  Primary:   Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

11.  Primary:   Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

12.  Primary:   Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

13.  Primary:   Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

14.  Primary:   Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)   [ Time Frame: Up to Day 7 ]

15.  Primary:   Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)   [ Time Frame: Up to Day 7 ]

16.  Secondary:   Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)   [ Time Frame: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2) ]

17.  Secondary:   Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)   [ Time Frame: Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3) ]

18.  Secondary:   Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)   [ Time Frame: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours ]

19.  Secondary:   Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)   [ Time Frame: Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours ]

20.  Secondary:   Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A)   [ Time Frame: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2). ]

21.  Secondary:   Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A)   [ Time Frame: Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2). ]

22.  Secondary:   Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B)   [ Time Frame: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. ]

23.  Secondary:   Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B)   [ Time Frame: 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. ]

24.  Secondary:   Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B)   [ Time Frame: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7 ]

25.  Secondary:   Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B)   [ Time Frame: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7 ]

26.  Secondary:   Measure of Oxygenation Index Upto Day 7 (Part B)   [ Time Frame: 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7 ]

27.  Secondary:   Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B)   [ Time Frame: Upto Day 3 ]

28.  Secondary:   Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B)   [ Time Frame: Day 4 and Day 7 ]

29.  Secondary:   Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B)   [ Time Frame: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5 ]

30.  Secondary:   Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B)   [ Time Frame: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5 ]

31.  Secondary:   Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B)   [ Time Frame: 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5 ]

32.  Secondary:   Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A)   [ Time Frame: Follow-up (Day 14) and follow-up (Day 28) ]

33.  Secondary:   Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B)   [ Time Frame: Follow-up (Day 14 )and follow-up (Day 28) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343



Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01597635     History of Changes
Other Study ID Numbers: 114622
First Submitted: January 26, 2012
First Posted: May 14, 2012
Results First Submitted: July 23, 2017
Results First Posted: September 28, 2017
Last Update Posted: September 28, 2017