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Study of GSK1278863 to Reduce Ischemic Events in Patients Undergoing Thoracic Aortic Aneurysm Repair

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ClinicalTrials.gov Identifier: NCT01920594
Recruitment Status : Completed
First Posted : August 12, 2013
Results First Posted : December 7, 2017
Last Update Posted : December 7, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Surgical Procedures
Interventions Drug: GSK1278863
Drug: Placebo
Enrollment 57
Recruitment Details This study was conducted across 10 centers in the United States and 2 centers in Canada from 31 October 2013 to 08 October 2014.
Pre-assignment Details A total of 55 participants were randomized in the study and were included in All Subjects Population. Participants were stratified according to intervention type (surgical or endovascular repair, with the latter limited to 50% of the total study population).
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description Eligible participants received GSK1278863 300 milligrams (mg) on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg once daily (QD) for 4 days starting from Day 0 (surgical day). Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Period Title: Overall Study
Started 27 28
Completed 20 25
Not Completed 7 3
Reason Not Completed
Adverse Event             4             2
Lost to Follow-up             1             0
Recovery             2             0
Investigator discretion             0             1
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo Total
Hide Arm/Group Description Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day). Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day). Total of all reporting groups
Overall Number of Baseline Participants 27 28 55
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
21 to 88 years Number Analyzed 27 participants 28 participants 55 participants
27
 100.0%
28
 100.0%
55
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 55 participants
Female
9
  33.3%
10
  35.7%
19
  34.5%
Male
18
  66.7%
18
  64.3%
36
  65.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 28 participants 55 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   3.7%
2
   7.1%
3
   5.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   7.4%
7
  25.0%
9
  16.4%
White
24
  88.9%
19
  67.9%
43
  78.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline to Peak in Cerebrospinal Fluid (CSF) S100 Beta Within 48 Hours Following Descending Thoracic Aorta/Thoracoabdominal Aortic Aneurysm (DTA/TAAA) Repair
Hide Description S100 beta is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF S100 beta. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) population comprised of all participants from whom PD data was available. For the change from Baseline assessment, only those with both evaluable Baseline and post-dose values (so that the change could be calculated) were included in the analysis.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Nanograms per liter (ng/L)
2748.19  (6212.035) 566.78  (1897.172)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0820
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2228.14
Confidence Interval (2-Sided) 95%
-292.84 to 4749.11
Estimation Comments The point estimate was calculated as least square (LS) mean difference (final values) of S-100B Protein [test] and S-100B Protein [reference].
2.Primary Outcome
Title Change From Baseline to Peak in CSF Glial Fibrillary Acidic Protein (GFAP) Within 48 Hours Following DTA/TAAA Repair
Hide Description GFAP is a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. CSF samples for the analysis of GFAP was collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF GFAP. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD population. For the change from Baseline assessment, only those with both evaluable Baseline and post-dose values (so that the change could be calculated) were included in the analysis.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Microgram per liter (µg/L)
1078.61  (2894.129) 283.03  (1092.448)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1997
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 777.95
Confidence Interval (2-Sided) 95%
-424.04 to 1979.94
Estimation Comments The point estimate was calculated as LS mean difference (final values) of GFAP [test] and GFAP [reference].
3.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, considered to be medically significant or is associated with liver injury and impaired liver function.
Time Frame Up to Follow-up (Day 45)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population comprised of all participants who received at least one dose of study drug (GSK1278863 or placebo).
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
26
  96.3%
23
  82.1%
Any SAEs
20
  74.1%
14
  50.0%
4.Secondary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Importance (PCI)
Hide Description Vital sign measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate. Criteria for vital sign values meeting PCI included: SBP < 70 millimeters of mercury (mmHg) and > 160 mmHg; DBP < 45 mmHg and > 110 mmHg. Data for participants with vital signs values outside the potential clinical importance range has been presented. Only those parameters for which at least one value of PCI was reported are summarized.
Time Frame Up to Follow-up (Day 45)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
SBP
2
   7.4%
1
   3.6%
DBP
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiography (ECG) Parameters
Hide Description Single 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate intervals. Data for participants with abnormal-clinical significant (CS) and abnormal-not clinically significant (NCS) ECG findings on post-operative Days 1, 2, 3, 4, 5, 6, 7 and during Follow-up Visits has been presented.
Time Frame Up to Follow-up (Day 45)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
Post-operative Day 1, Abnormal-NCS Number Analyzed 26 participants 25 participants
18
  69.2%
18
  72.0%
Post-operative Day 2, Abnormal-NCS Number Analyzed 24 participants 24 participants
18
  75.0%
17
  70.8%
Post-operative Day 3, Abnormal-NCS Number Analyzed 22 participants 22 participants
17
  77.3%
16
  72.7%
Post-operative Day 3, Abnormal-CS Number Analyzed 22 participants 22 participants
1
   4.5%
1
   4.5%
Post-operative Day 4, Abnormal-NCS Number Analyzed 18 participants 22 participants
13
  72.2%
18
  81.8%
Post-operative Day 5, Abnormal-NCS Number Analyzed 17 participants 21 participants
14
  82.4%
17
  81.0%
Post-operative Day 6, Abnormal-NCS Number Analyzed 19 participants 16 participants
14
  73.7%
10
  62.5%
Post-operative Day 7, Abnormal-NCS Number Analyzed 22 participants 22 participants
15
  68.2%
15
  68.2%
Follow-up, Abnormal-NCS Number Analyzed 15 participants 22 participants
11
  73.3%
13
  59.1%
6.Secondary Outcome
Title Number of Participants With Clinical Chemistry Parameters of PCI
Hide Description Blood samples for assessment of clinical chemistry parameters aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, blood urea nitrogen (BUN), creatinine, glucose, sodium, creatine phosphokinase, potassium, chloride, total carbon dioxide, calcium, total and direct bilirubin, uric acid, albumin and total protein was done at Randomization, Day 0 (done prior to 100 mg on-call dosing), 1, 2, 3, 4, 5, 6 and 7. Only those parameters for which at least one value of PCI was reported are summarized. Data for participants with clinical chemistry values outside the PCI range has been presented.
Time Frame Up to post-operative Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
19
  70.4%
18
  64.3%
7.Secondary Outcome
Title Number of Participants With Hematology Parameters of PCI
Hide Description Blood samples for assessment of hematology parameters platelet count, red blood cell count, white blood cell count, reticulocyte count, hemoglobin, hematocrit, mean corpuscle volume, mean corpuscle hemoglobin, mean corpuscle hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils and basophils was done at Randomization, Day 0 (done prior to 100 mg on-call dosing), 1, 2, 3, 4, 5, 6 and 7. Only those parameters for which at least one value of PCI was reported are summarized. Data for participants with hematology values outside the PCI range has been presented.
Time Frame Up to post-operative Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
25
  92.6%
16
  57.1%
8.Secondary Outcome
Title Change From Baseline in Area Under Curve (AUC) for CSF S100 Beta to 48 Hours
Hide Description S100 beta was a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. AUC for CSF S100 beta from Baseline to 48 hours following DTA/TAAA repair was assessed to measure central nervous system injury. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
Time Frame Baseline(Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*nanogram per liter (hour*ng/L)
17263.25
(316.40%)
9758.27
(221.85%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1530
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate of comparison (Ratio)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
0.80 to 3.90
Estimation Comments The point estimate was calculated as Geometric mean ratio of S-100B[test] and S-100B[reference].
9.Secondary Outcome
Title Change From Baseline in AUC for CSF GFAP to 48 Hours
Hide Description GFAP was a CSF biomarker that rise significantly in participants with neurologic injury following DTA/TAAA surgery. AUC for CSF GFAP from Baseline to 48 hours following DTA/TAAA repair was assessed to measure central nervous system injury. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
Time Frame Baseline(Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*microgram per liter (hour*µg/L)
182.35
(15899.84%)
58.32
(1413.66%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1377
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimate of comparison (Ratio)
Estimated Value 3.13
Confidence Interval (2-Sided) 95%
0.69 to 14.26
Estimation Comments The point estimate was calculated as Geometric mean ratio of GFAP[test] and GFAP[reference].
10.Secondary Outcome
Title Change From Baseline to Peak in CSF Biomarker Erythropoietin Within 48 Hours Following DTA/TAAA Repair
Hide Description CSF biomarker erythropoietin samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF erythropoietin. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD population. For the change from Baseline assessment, only those with both evaluable Baseline and post-dose values (so that the change could be calculated) were included in the analysis.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: International units per liter (IU/L)
1.34  (137.411) 0.61  (1.582)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 34.56
Confidence Interval (2-Sided) 95%
21.95 to 47.17
Estimation Comments The point estimate was calculated as LS mean difference final values of Erythropoietin[test] and Erythropoietin[reference].
11.Secondary Outcome
Title Change From Baseline to Peak in CSF Biomarker Lactate Dehydrogenase Within 48 Hours Following DTA/TAAA Repair
Hide Description CSF biomarker lactate dehydrogenase samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF lactate dehydrogenase. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population. For the change from Baseline assessment, only those with both evaluable Baseline and post-dose values (so that the change could be calculated) were included in the analysis.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Millimoles per liter (mmol/L)
1.82  (2.021) 1.28  (1.160)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2404
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
-0.37 to 1.45
Estimation Comments The point estimate was calculated as LS mean difference final values of Lactate Dehydrogenase[test] and Lactate Dehydrogenase[reference].
12.Secondary Outcome
Title Change From Baseline to Peak in CSF Biomarker Tau Protein Within 48 Hours Following DTA/TAAA Repair
Hide Description CSF biomarker tau protein samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF tau protein. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
Time Frame Baseline (Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population. For the change from Baseline assessment, only those with both evaluable Baseline and post-dose values (so that the change could be calculated) were included in the analysis.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: ng/L
1729.25  (2177.526) 751.21  (1053.951)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0526
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 925.88
Confidence Interval (2-Sided) 95%
-10.73 to 1862.49
Estimation Comments The point estimate was calculated as LS mean difference final values of Tau Protein[test] and Tau Protein[reference].
13.Secondary Outcome
Title Change From Baseline to Peak in CSF Biomarker Neuron-specific Enolase (NSE) Within 48 Hours Following DTA/TAAA Repair
Hide Description CSF biomarker NSE samples were collected for the analysis of ischemic neurologic injury. CSF samples were collected at Baseline and within 48 hours following DTA/TAAA repair to assess peak change from Baseline in CSF NSE. Baseline was defined at Day 0. Change from Baseline was calculated as post-Baseline minus Baseline value.
Time Frame Baseline (Day 0) to 48 hours following DTA/TAAA repair
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population. For the change from Baseline assessment, only those with both evaluable Baseline and post-dose values (so that the change could be calculated) were included in the analysis.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: µg/L
9.31  (9.717) 5.65  (7.214)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0893
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.11
Confidence Interval (2-Sided) 95%
-0.65 to 8.87
Estimation Comments The point estimate was calculated as LS mean difference final values of Neuron Specific Enolase[test] and Neuron Specific Enolase[reference].
14.Secondary Outcome
Title Number of Participants With Neurologic Outcomes Assessed by the National Institutes of Health Stroke Scale (NIHSS)
Hide Description The NIHSS was a systematic assessment tool that provided a quantitative measure of stroke-related neurologic deficit. A trained observer rates the participant’s ability to answer questions and perform activities. Ratings for each item are scored with 0 as normal, and there was an allowance for untestable items. The NIHSS scores were categorized as: No event (NIHSS score=0), Mild (NIHSS score 1–4), Moderate (NIHSS score 5-15), or Severe (NIHSS score >15). The single participant assessment required less than 10 minutes to complete. Data for participants with NIHSS administrated at surgical day, post-operative Day 1, Day 2, Day 7 and Follow-up Visit has been reported.
Time Frame Surgical Day (Day 0), Post-operative Day 1, 2, 7 and follow-up (Day 45)
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Hide Analysis Population Description
PD population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
Surgical Day, No event (Score=0) Number Analyzed 27 participants 26 participants
27
 100.0%
23
  88.5%
Surgical Day, Mild (Score 1-4) Number Analyzed 27 participants 26 participants
0
   0.0%
3
  11.5%
Post-operative Day 1, No event (Score=0) Number Analyzed 25 participants 23 participants
11
  44.0%
14
  60.9%
Post-operative Day 1, Mild (Score 1-4) Number Analyzed 25 participants 23 participants
4
  16.0%
7
  30.4%
Post-operative Day 1, Moderate (Score 5-15) Number Analyzed 25 participants 23 participants
4
  16.0%
1
   4.3%
Post-operative Day 1, Severe (Score >15) Number Analyzed 25 participants 23 participants
6
  24.0%
1
   4.3%
Post-operative Day 2, No event (Score=0) Number Analyzed 24 participants 22 participants
11
  45.8%
15
  68.2%
Post-operative Day 2, Mild (Score 1-4) Number Analyzed 24 participants 22 participants
4
  16.7%
3
  13.6%
Post-operative Day 2, Moderate (Score 5-15) Number Analyzed 24 participants 22 participants
3
  12.5%
3
  13.6%
Post-operative Day 2, Severe (Score >15) Number Analyzed 24 participants 22 participants
6
  25.0%
1
   4.5%
Post-operative Day 7, No event (Score=0) Number Analyzed 20 participants 24 participants
10
  50.0%
16
  66.7%
Post-operative Day 7, Mild (Score 1-4) Number Analyzed 20 participants 24 participants
2
  10.0%
7
  29.2%
Post-operative Day 7, Moderate (Score 5-15) Number Analyzed 20 participants 24 participants
4
  20.0%
1
   4.2%
Post-operative Day 7, Severe (Score >15) Number Analyzed 20 participants 24 participants
4
  20.0%
0
   0.0%
Follow-up, No event (Score=0) Number Analyzed 18 participants 25 participants
13
  72.2%
17
  68.0%
Follow-up, Mild (Score 1-4) Number Analyzed 18 participants 25 participants
1
   5.6%
6
  24.0%
Follow-up, Moderate (Score 5-15) Number Analyzed 18 participants 25 participants
4
  22.2%
2
   8.0%
15.Secondary Outcome
Title Number of Participants With Neurologic Outcomes Assessed by Modified Rankin Scale (mRS)
Hide Description The mRS was a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS was a 6 point disability scale with possible scores ranging from 0 up to 5. A separate category (of 6) was added for participants who died. The mRS scores were categorized as mild (mRS score 0-1), moderate (mRS score 2-3), or severe (mRS score >=4).
Time Frame Post-operative Day 7 and follow-up (Day 45)
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Hide Analysis Population Description
PD population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
Post-operative Day 7, Mild (Score 0-1) Number Analyzed 20 participants 24 participants
9
  45.0%
11
  45.8%
Post-operative Day 7, Moderate (Score 2-3) Number Analyzed 20 participants 24 participants
1
   5.0%
8
  33.3%
Post-operative Day 7, Severe (Score >=4) Number Analyzed 20 participants 24 participants
10
  50.0%
5
  20.8%
Follow-up, Mild (Score 0-1) Number Analyzed 18 participants 25 participants
8
  44.4%
14
  56.0%
Follow-up, Moderate (Score 2-3) Number Analyzed 18 participants 25 participants
4
  22.2%
7
  28.0%
Follow-up, Severe (Score >=4) Number Analyzed 18 participants 25 participants
6
  33.3%
4
  16.0%
16.Secondary Outcome
Title Number of Participants With Neurologic Outcomes Assessed by the American Spinal Injury Association (ASIA) Lower Extremity Motor Outcome Scale
Hide Description The ASIA score was developed by the American Spinal Injury Association for the neurologic assessment of participants with a spinal injury. In this study, only the ASIA lower extremity motor score was assessed. This comprised five muscle groups scored from 0-5 on both the left and right lower extremities, for a maximal total score of 50. The ASIA scores were categorized as: mild (ASIA score 41-50), moderate (ASIA score 26-40), or severe (ASIA score <=25).
Time Frame Surgical Day (Day 0), Post-operative Day 1, 2, 7 and follow-up (Day 45)
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Hide Analysis Population Description
PD population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
Surgical Day, Mild (Score 41-50) Number Analyzed 27 participants 26 participants
26
  96.3%
26
 100.0%
Surgical Day, Moderate (Score 26-40) Number Analyzed 27 participants 26 participants
1
   3.7%
0
   0.0%
Post-operative Day 1, Mild (Score 41-50) Number Analyzed 25 participants 23 participants
15
  60.0%
19
  82.6%
Post-operative Day 1, Moderate (Score 26-40) Number Analyzed 25 participants 23 participants
2
   8.0%
2
   8.7%
Post-operative Day 1, Severe (Score <=25) Number Analyzed 25 participants 23 participants
8
  32.0%
2
   8.7%
Post-operative Day 2, Mild (Score 41-50) Number Analyzed 23 participants 22 participants
14
  60.9%
21
  95.5%
Post-operative Day 2, Moderate (Score 26-40) Number Analyzed 23 participants 22 participants
1
   4.3%
0
   0.0%
Post-operative Day 2, Severe (Score <=25) Number Analyzed 23 participants 22 participants
8
  34.8%
1
   4.5%
Post-operative Day 7, Mild (Score 41-50) Number Analyzed 20 participants 24 participants
13
  65.0%
22
  91.7%
Post-operative Day 7, Moderate (Score 26-40) Number Analyzed 20 participants 24 participants
1
   5.0%
1
   4.2%
Post-operative Day 7, Severe (Score <=25) Number Analyzed 20 participants 24 participants
6
  30.0%
1
   4.2%
Follow-up, Mild (Score 41-50) Number Analyzed 18 participants 25 participants
14
  77.8%
24
  96.0%
Follow-up, Moderate (Score 26-40) Number Analyzed 18 participants 25 participants
2
  11.1%
0
   0.0%
Follow-up, Severe (Score <=25) Number Analyzed 18 participants 25 participants
2
  11.1%
1
   4.0%
17.Secondary Outcome
Title Number of Participants With Clinical Composite of All Cause Mortality, Stroke, Spinal Infarction, MI, Need for Dialysis/Sustained Doubling of Serum Creatinine
Hide Description The clinical composite event rate included all-cause mortality (death), stroke, spinal infarction (paraplegia which was due to spinal infarct a result of the surgery, myocardial infarction, and the need for dialysis or sustained doubling of serum creatinine (acute kidney injury). The clinical composite endpoint used a first occurrence approach, i.e. a composite event was recorded at the time of first occurrence of any component of the composite.
Time Frame Up to Follow-up (Day 45)
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All Subjects Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
Acute Kidney Injury
13
  48.1%
10
  35.7%
Myocardial Infarction
1
   3.7%
0
   0.0%
Paraplegia
6
  22.2%
4
  14.3%
Stroke
1
   3.7%
2
   7.1%
Death
6
  22.2%
2
   7.1%
Composite Above
16
  59.3%
12
  42.9%
18.Secondary Outcome
Title Assessment in AUC for Markers of Ischemic Organ Injury Including Tropinin Within 48 Hours
Hide Description AUC from 8 hours post surgery (up to 48 hours post surgery) was derived for markers of ischemic organ injury troponin I and troponin T. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Baseline (Day 0) and 8 to 48 hours following DTA/TAAA repair
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Hide Analysis Population Description
PD population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg*hour/L
Troponin I Number Analyzed 19 participants 17 participants
13.29
(0.615%)
7.23
(0.650%)
Troponin T Number Analyzed 8 participants 11 participants
3.14
(0.879%)
4.19
(0.750%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments For Troponin I
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5012
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric mean
Estimated Value 1.84
Confidence Interval (2-Sided) 95%
0.30 to 11.32
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection GSK1278863 300 mg Loading + 100 mg QD, Placebo
Comments For Troponin T
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8053
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric mean
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.07 to 8.57
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Number of Participants With Composite Index of All Cause Mortality and Disability (NIHSS>5/ASIA<40)
Hide Description The NIHSS was a systematic assessment tool that provided a quantitative measure of stroke-related neurologic deficit. Ratings for each item are scored with 0 as normal, and there was an allowance for untestable items. The NIHSS scores were categorized as: No event (NIHSS score=0), Mild (NIHSS score 1–4), Moderate (NIHSS score 5-15), or Severe (NIHSS score >15). The ASIA score was developed by the American Spinal Injury Association for the neurologic assessment of participants with a spinal injury. In this study, only the ASIA lower extremity motor score was assessed. This comprised five muscle groups scored from 0-5 on both the left and right lower extremities, for a maximal total score of 50. The ASIA scores were categorized as: mild (ASIA score 41-50), moderate (ASIA score 26-40), or severe (ASIA score <=25). “Composite above” includes participants with NIHSS>5 or ASIA<40 at the 30-day Follow-up or Death.
Time Frame Up to Follow-up (Day 45)
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Hide Analysis Population Description
PD Population.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27 28
Measure Type: Count of Participants
Unit of Measure: Participants
ASIA <40
4
  14.8%
1
   3.6%
NIHSS >5
4
  14.8%
2
   7.1%
Death
6
  22.2%
2
   7.1%
Composite Above
11
  40.7%
4
  14.3%
20.Secondary Outcome
Title Pharmacokinetic (PK) Parameters in Blood: AUC(0-t) of GSK1278863
Hide Description Blood samples for PK analysis AUC(0-t) were collected at pre-dose (prior to the 100 mg dose), 1-3 hours after study drug was administered and then every 5 hours for 24 hours. On Days 1 and 3 samples were collected at pre-dose then 1, 3, 8 and 24 hours post dose. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*ng/mL
Blood, Surgical Day Number Analyzed 26 participants
3591.449
(50.23%)
Blood, Post-operative Day 1 Number Analyzed 27 participants
2858.165
(129.26%)
Blood, Post-operative Day 3 Number Analyzed 23 participants
3710.790
(115.20%)
21.Secondary Outcome
Title PK Parameters in CSF: AUC(0-t) of GSK1278863
Hide Description CSF samples were collected immediately after the lumbar drain was placed, just prior to PNI, and 2, 24, 36 and 48 hours post PNI. In participants that developed spinal ischemia, the CSF drain was potentially maintained for longer than 48 hours. In that instance, daily CSF samples for PK were collected until the drain was removed. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI
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Hide Analysis Population Description
PK Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*ng/mL
37.340
(156.10%)
22.Secondary Outcome
Title PK Parameters in Blood: Maximum Observed Concentration (Cmax) of GSK1278863
Hide Description Blood samples for PK analysis AUC(0-t) were collected at pre-dose (prior to the 100 mg dose), 1-3 hours after study drug was administered and then every 5 hours for 24 hours. On Days 1 and 3 samples were collected at pre-dose then 1, 3, 8 and 24 hours post dose. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ng/mL
Blood, Surgical Day Number Analyzed 26 participants
705.701
(83.43%)
Blood, Post-operative Day 1 Number Analyzed 27 participants
358.518
(192.32%)
Blood, Post-operative Day 3 Number Analyzed 23 participants
779.801
(110.20%)
23.Secondary Outcome
Title PK Parameters in CSF: Cmax of GSK1278863
Hide Description CSF samples were collected immediately after the lumbar drain was placed, just prior to PNI, and 2, 24, 36 and 48 hours post PNI. In participants that developed spinal ischemia, the CSF drain was potentially maintained for longer than 48 hours. In that instance, daily CSF samples for PK were collected until the drain was removed. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ng/L
2.364
(105.24%)
24.Secondary Outcome
Title PK Parameters in Blood: Time of Occurrence of Cmax (Tmax) of GSK1278863
Hide Description Blood samples for PK analysis AUC(0-t) were collected at pre-dose (prior to the 100 mg dose), 1-3 hours after study drug was administered and then every 5 hours for 24 hours. On Days 1 and 3 samples were collected at pre-dose then 1, 3, 8 and 24 hours post dose. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Pre-dose, 1 to 3 hours post-dose, every 5 hours for 24 hours, 1, 3, 8 and 24 hours post-dose on Day 1 and 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: Hours
Blood, Surgical day Number Analyzed 26 participants
1.725
(0.00 to 16.38)
Blood, Post-operative Day 1 Number Analyzed 27 participants
3.017
(0.02 to 24.43)
Blood, Post-operative Day 3 Number Analyzed 23 participants
3.017
(0.77 to 8.18)
25.Secondary Outcome
Title PK Parameters in CSF: Tmax of GSK1278863
Hide Description CSF samples were collected immediately after the lumbar drain was placed, just prior to PNI, and 2, 24, 36 and 48 hours post PNI. In participants that developed spinal ischemia, the CSF drain was potentially maintained for longer than 48 hours. In that instance, daily CSF samples for PK were collected until the drain was removed. AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Prior to potential neurological ischemia (PNI), 2, 24, 36 and 48 hours post PNI
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD
Hide Arm/Group Description:
Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
Overall Number of Participants Analyzed 26
Mean (95% Confidence Interval)
Unit of Measure: Hours
15.326
(8.097 to 22.554)
Time Frame AEs were collected up to Follow-up (Day 45).
Adverse Event Reporting Description All Subjects Population was used.
 
Arm/Group Title GSK1278863 300 mg Loading + 100 mg QD Placebo
Hide Arm/Group Description Eligible participants received GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day). Eligible participants received Placebo matching GSK1278863 300 mg on Day -1 (12 +/- 4 hours prior to planned surgery) as a loading dose followed by Placebo matching GSK1278863 100 mg QD for 4 days starting from Day 0 (surgical day).
All-Cause Mortality
GSK1278863 300 mg Loading + 100 mg QD Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   6/27 (22.22%)   2/28 (7.14%) 
Show Serious Adverse Events Hide Serious Adverse Events
GSK1278863 300 mg Loading + 100 mg QD Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   20/27 (74.07%)   14/28 (50.00%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  4/27 (14.81%)  0/28 (0.00%) 
Disseminated intravascular coagulation  1  1/27 (3.70%)  1/28 (3.57%) 
Heparin-induced thrombocytopenia  1  1/27 (3.70%)  0/28 (0.00%) 
Leukocytosis  1  0/27 (0.00%)  1/28 (3.57%) 
Cardiac disorders     
Cardio-respiratory arrest  1  1/27 (3.70%)  1/28 (3.57%) 
Ventricular fibrillation  1  2/27 (7.41%)  0/28 (0.00%) 
Cardiogenic shock  1  0/27 (0.00%)  1/28 (3.57%) 
Sinus tachycardia  1  0/27 (0.00%)  1/28 (3.57%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  2/27 (7.41%)  0/28 (0.00%) 
Ileus  1  1/27 (3.70%)  0/28 (0.00%) 
Retroperitoneal haematoma  1  0/27 (0.00%)  1/28 (3.57%) 
Upper gastrointestinal haemorrhage  1  0/27 (0.00%)  1/28 (3.57%) 
Volvulus  1  1/27 (3.70%)  0/28 (0.00%) 
General disorders     
Multi-organ failure  1  4/27 (14.81%)  0/28 (0.00%) 
Ischaemic ulcer  1  1/27 (3.70%)  0/28 (0.00%) 
Hepatobiliary disorders     
Hepatic failure  1  1/27 (3.70%)  0/28 (0.00%) 
Infections and infestations     
Septic shock  1  1/27 (3.70%)  1/28 (3.57%) 
Cystitis klebsiella  1  1/27 (3.70%)  0/28 (0.00%) 
Incision site infection  1  0/27 (0.00%)  1/28 (3.57%) 
Pneumonia klebsiella  1  1/27 (3.70%)  0/28 (0.00%) 
Wound infection staphylococcal  1  1/27 (3.70%)  0/28 (0.00%) 
Injury, poisoning and procedural complications     
Post procedural haemorrhage  1  1/27 (3.70%)  1/28 (3.57%) 
Postoperative respiratory failure  1  2/27 (7.41%)  0/28 (0.00%) 
Internal injury  1  1/27 (3.70%)  0/28 (0.00%) 
Postoperative thoracic procedure complication  1  0/27 (0.00%)  1/28 (3.57%) 
Spinal cord injury  1  1/27 (3.70%)  0/28 (0.00%) 
Subdural haematoma  1  0/27 (0.00%)  1/28 (3.57%) 
Investigations     
Pulse absent  1  1/27 (3.70%)  0/28 (0.00%) 
Red blood cells CSF positive  1  0/27 (0.00%)  1/28 (3.57%) 
Transaminases increased  1  1/27 (3.70%)  0/28 (0.00%) 
Metabolism and nutrition disorders     
Lactic acidosis  1  1/27 (3.70%)  0/28 (0.00%) 
Nervous system disorders     
Spinal cord ischaemia  1  2/27 (7.41%)  1/28 (3.57%) 
Cerebrospinal fluid leakage  1  0/27 (0.00%)  1/28 (3.57%) 
Cerebrovascular accident  1  1/27 (3.70%)  0/28 (0.00%) 
Monoplegia  1  1/27 (3.70%)  0/28 (0.00%) 
Neurological decompensation  1  1/27 (3.70%)  0/28 (0.00%) 
Paraparesis  1  0/27 (0.00%)  1/28 (3.57%) 
Paraplegia  1  1/27 (3.70%)  0/28 (0.00%) 
Subarachnoid haemorrhage  1  0/27 (0.00%)  1/28 (3.57%) 
Renal and urinary disorders     
Renal failure acute  1  5/27 (18.52%)  0/28 (0.00%) 
Renal failure  1  2/27 (7.41%)  0/28 (0.00%) 
Renal artery thrombosis  1  1/27 (3.70%)  0/28 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  3/27 (11.11%)  1/28 (3.57%) 
Acute respiratory distress syndrome  1  1/27 (3.70%)  0/28 (0.00%) 
Acute respiratory failure  1  1/27 (3.70%)  0/28 (0.00%) 
Chronic respiratory failure  1  0/27 (0.00%)  1/28 (3.57%) 
Haemothorax  1  1/27 (3.70%)  0/28 (0.00%) 
Hypoxia  1  1/27 (3.70%)  0/28 (0.00%) 
Pneumonia aspiration  1  1/27 (3.70%)  0/28 (0.00%) 
Pneumothorax  1  1/27 (3.70%)  0/28 (0.00%) 
Pulmonary embolism  1  1/27 (3.70%)  0/28 (0.00%) 
Pulmonary haemorrhage  1  1/27 (3.70%)  0/28 (0.00%) 
Pulmonary oedema  1  0/27 (0.00%)  1/28 (3.57%) 
Vascular disorders     
Peripheral ischaemia  1  4/27 (14.81%)  0/28 (0.00%) 
Aortic aneurysm rupture  1  1/27 (3.70%)  0/28 (0.00%) 
Arterial haemorrhage  1  1/27 (3.70%)  0/28 (0.00%) 
Deep vein thrombosis  1  1/27 (3.70%)  0/28 (0.00%) 
Embolism  1  1/27 (3.70%)  0/28 (0.00%) 
Haemodynamic instability  1  1/27 (3.70%)  0/28 (0.00%) 
Peripheral artery thrombosis  1  1/27 (3.70%)  0/28 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GSK1278863 300 mg Loading + 100 mg QD Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   20/27 (74.07%)   19/28 (67.86%) 
Blood and lymphatic system disorders     
Anaemia  1  0/27 (0.00%)  4/28 (14.29%) 
Haemorrhagic anaemia  1  3/27 (11.11%)  1/28 (3.57%) 
Leukocytosis  1  2/27 (7.41%)  2/28 (7.14%) 
Thrombocytopenia  1  2/27 (7.41%)  1/28 (3.57%) 
Coagulopathy  1  2/27 (7.41%)  0/28 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  4/27 (14.81%)  3/28 (10.71%) 
Bradycardia  1  0/27 (0.00%)  2/28 (7.14%) 
Sinus tachycardia  1  0/27 (0.00%)  2/28 (7.14%) 
Supraventricular tachycardia  1  0/27 (0.00%)  2/28 (7.14%) 
Gastrointestinal disorders     
Nausea  1  5/27 (18.52%)  5/28 (17.86%) 
Vomiting  1  1/27 (3.70%)  4/28 (14.29%) 
Constipation  1  2/27 (7.41%)  2/28 (7.14%) 
General disorders     
Pain  1  2/27 (7.41%)  2/28 (7.14%) 
Pyrexia  1  2/27 (7.41%)  1/28 (3.57%) 
Catheter site pain  1  0/27 (0.00%)  2/28 (7.14%) 
Infections and infestations     
Urinary tract infection  1  3/27 (11.11%)  3/28 (10.71%) 
Respiratory tract infection  1  2/27 (7.41%)  0/28 (0.00%) 
Injury, poisoning and procedural complications     
Procedural pain  1  2/27 (7.41%)  3/28 (10.71%) 
Post lumbar puncture syndrome  1  1/27 (3.70%)  3/28 (10.71%) 
Wound complication  1  2/27 (7.41%)  2/28 (7.14%) 
Investigations     
Troponin increased  1  3/27 (11.11%)  0/28 (0.00%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  2/27 (7.41%)  3/28 (10.71%) 
Hypophosphataemia  1  3/27 (11.11%)  2/28 (7.14%) 
Fluid overload  1  1/27 (3.70%)  2/28 (7.14%) 
Hypocalcaemia  1  1/27 (3.70%)  2/28 (7.14%) 
Hyperglycaemia  1  0/27 (0.00%)  2/28 (7.14%) 
Hypernatraemia  1  2/27 (7.41%)  0/28 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/27 (3.70%)  5/28 (17.86%) 
Nervous system disorders     
Headache  1  3/27 (11.11%)  4/28 (14.29%) 
Vocal cord paralysis  1  1/27 (3.70%)  2/28 (7.14%) 
Psychiatric disorders     
Anxiety  1  1/27 (3.70%)  2/28 (7.14%) 
Confusional state  1  0/27 (0.00%)  2/28 (7.14%) 
Renal and urinary disorders     
Renal failure acute  1  4/27 (14.81%)  7/28 (25.00%) 
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  2/27 (7.41%)  4/28 (14.29%) 
Atelectasis  1  1/27 (3.70%)  3/28 (10.71%) 
Hypoxia  1  2/27 (7.41%)  2/28 (7.14%) 
Vascular disorders     
Hypertension  1  3/27 (11.11%)  6/28 (21.43%) 
Hypotension  1  4/27 (14.81%)  5/28 (17.86%) 
Ischaemia  1  2/27 (7.41%)  0/28 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01920594     History of Changes
Other Study ID Numbers: 116097
First Submitted: August 8, 2013
First Posted: August 12, 2013
Results First Submitted: September 18, 2017
Results First Posted: December 7, 2017
Last Update Posted: December 7, 2017