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

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.
ClinicalTrials.gov Identifier: NCT01597635
Recruitment Status : Completed
First Posted : May 14, 2012
Results First Posted : September 28, 2017
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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)
Enrollment 44
Recruitment Details 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 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.
Arm/Group Title Part A Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description 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. Eligible participants received intravenous matching placebo (saline solution) twice daily (BID) as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Period Title: Part A
Started 5 0 0
Completed 2 0 0
Not Completed 3 0 0
Reason Not Completed
Adverse Event             3             0             0
Period Title: Part B
Started 0 20 19
Completed 0 14 15
Not Completed 0 6 4
Reason Not Completed
Adverse Event             0             0             1
Protocol Violation             0             1             0
Protocol-defined stopping criteria             0             4             3
Withdrawal by Subject             0             1             0
Arm/Group Title Part A Part B (Placebo BID) Part B (GSK2586881 BID) Total
Hide Arm/Group Description 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. Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. 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 of all reporting groups
Overall Number of Baseline Participants 5 20 19 44
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
18-80 years Number Analyzed 5 participants 20 participants 19 participants 44 participants
5
 100.0%
20
 100.0%
19
 100.0%
44
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 20 participants 19 participants 44 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 20 participants 19 participants 44 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%
1.Primary Outcome
Title Heart Rate Assessments Upto Day 7 (Part B)
Hide Description Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population was defined as all participants in Part B who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Heart rate on Day 1 at Pre-dose Number Analyzed 20 participants 19 participants
87.4  (16.32) 97.7  (16.25)
Heart rate on Day 1 at 0.5 hours Number Analyzed 20 participants 19 participants
87.9  (17.08) 95.3  (15.10)
Heart rate on Day 1 at 2 hours Number Analyzed 20 participants 19 participants
88.8  (18.22) 94.7  (17.59)
Heart rate on Day 1 at 6 hours Number Analyzed 20 participants 19 participants
90.0  (18.03) 96.5  (18.58)
Heart rate on Day 1 at 12 hours Number Analyzed 20 participants 19 participants
87.6  (20.60) 97.1  (18.46)
Heart rate on Day 2 at 0 hours Number Analyzed 20 participants 19 participants
92.2  (19.02) 93.4  (16.98)
Heart rate on Day 3 at 0 hours Number Analyzed 18 participants 19 participants
93.3  (19.20) 97.7  (14.11)
Heart rate on Day 3 at 0.5 hours Number Analyzed 18 participants 19 participants
91.7  (16.29) 97.2  (12.81)
Heart rate on Day 3 at 2 hours Number Analyzed 18 participants 19 participants
93.2  (16.51) 95.2  (13.31)
Heart rate on Day 3 at 6 hours Number Analyzed 18 participants 19 participants
93.2  (16.63) 97.5  (14.44)
Heart rate on Day 3 at 12 hours Number Analyzed 18 participants 19 participants
93.8  (20.12) 93.6  (16.08)
Heart rate on Day 3 at 18 hours Number Analyzed 17 participants 17 participants
98.1  (19.34) 88.9  (15.69)
Heart rate on Day 3 at 24 hours Number Analyzed 17 participants 18 participants
90.8  (15.46) 95.1  (13.25)
Heart rate at follow-up Day 7 Number Analyzed 16 participants 15 participants
91.6  (19.06) 94.2  (15.17)
2.Primary Outcome
Title Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)
Hide Description Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: Millimeters of merucry
Diastolic blood pressure on Day 1 at Pre-dose Number Analyzed 20 participants 19 participants
64.7  (12.86) 53.9  (10.36)
Diastolic blood pressure on Day 1 at 0.5 hours Number Analyzed 20 participants 18 participants
64.4  (13.75) 54.3  (11.39)
Diastolic blood pressure on Day 1 at 2 hours Number Analyzed 20 participants 19 participants
64.4  (12.59) 54.8  (9.60)
Diastolic blood pressure on Day 1 at 6 hours Number Analyzed 20 participants 19 participants
63.4  (12.08) 57.1  (9.21)
Diastolic blood pressure on Day 1 at 12 hours Number Analyzed 20 participants 19 participants
64.3  (12.78) 57.6  (10.05)
Diastolic blood pressure on Day 2 at 0 hours Number Analyzed 20 participants 19 participants
67.0  (15.17) 57.0  (10.22)
Diastolic blood pressure on Day 3 at 0 hours Number Analyzed 18 participants 18 participants
63.9  (14.50) 62.7  (14.03)
Diastolic blood pressure on Day 3 at 0.5 hours Number Analyzed 17 participants 19 participants
65.6  (13.21) 61.1  (12.83)
Diastolic blood pressure on Day 3 at 2 hours Number Analyzed 18 participants 19 participants
65.2  (10.34) 58.1  (11.20)
Diastolic blood pressure on Day 3 at 6 hours Number Analyzed 17 participants 19 participants
65.2  (13.83) 62.2  (16.59)
Diastolic blood pressure on Day 3 at 12 hours Number Analyzed 18 participants 19 participants
70.0  (16.40) 60.6  (13.20)
Diastolic blood pressure on Day 3 at 18 hours Number Analyzed 17 participants 17 participants
73.2  (16.31) 61.8  (10.50)
Diastolic blood pressure on Day 3 at 24 hours Number Analyzed 17 participants 18 participants
66.4  (15.19) 61.1  (13.06)
Diastolic blood pressure on follow-up Day 7 Number Analyzed 16 participants 15 participants
66.4  (11.58) 62.7  (8.52)
Systolic blood pressure on Day 1 at Pre-dose Number Analyzed 20 participants 19 participants
122.0  (18.97) 106.1  (12.68)
Systolic blood pressure on Day 1 at 0.5 hours Number Analyzed 20 participants 18 participants
118.8  (20.01) 105.7  (12.66)
Systolic blood pressure on Day 1 at 2 hours Number Analyzed 20 participants 19 participants
122.9  (14.85) 107.5  (20.49)
Systolic blood pressure on Day 1 at 6 hours Number Analyzed 20 participants 19 participants
121.6  (17.80) 118.7  (16.41)
Systolic blood pressure on Day 1 at 12 hours Number Analyzed 20 participants 19 participants
122.9  (21.88) 116.9  (24.33)
Systolic blood pressure on Day 2 at 0 hours Number Analyzed 20 participants 19 participants
131.6  (23.68) 114.8  (18.94)
Systolic blood pressure on Day 3 at 0 hours Number Analyzed 18 participants 18 participants
124.4  (16.32) 125.2  (23.70)
Systolic blood pressure on Day 3 at 0.5 hours Number Analyzed 17 participants 19 participants
127.1  (15.76) 121.9  (23.60)
Systolic blood pressure on Day 3 at 2 hours Number Analyzed 18 participants 19 participants
125.2  (14.77) 118.5  (20.87)
Systolic blood pressure on Day 3 at 6 hours Number Analyzed 17 participants 19 participants
127.8  (19.01) 118.5  (19.60)
Systolic blood pressure on Day 3 at 12 hours Number Analyzed 18 participants 19 participants
130.2  (21.95) 123.2  (24.61)
Systolic blood pressure on Day 3 at 18 hours Number Analyzed 17 participants 17 participants
137.5  (23.92) 129.0  (17.45)
Systolic blood pressure on Day 3 at 24 hours Number Analyzed 17 participants 18 participants
128.8  (20.43) 130.3  (24.97)
Systolic blood pressure on follow-up Day 7 Number Analyzed 16 participants 15 participants
129.1  (22.22) 129.9  (17.92)
3.Primary Outcome
Title Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)
Hide Description Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: millisecond
PR interval on Day 1,Pre-dose Number Analyzed 5 participants 8 participants
136.8  (24.19) 139.0  (25.09)
PR interval on Day 3,12 hours Number Analyzed 13 participants 16 participants
128.5  (42.09) 149.3  (19.76)
PR interval at follow-up Number Analyzed 4 participants 13 participants
140.4  (17.81) 144.8  (20.73)
QRS duration on Day 1,Pre-dose Number Analyzed 5 participants 8 participants
98.0  (9.27) 95.5  (16.62)
QRS duration on Day 3,12 hours Number Analyzed 13 participants 16 participants
82.8  (8.66) 98.8  (15.86)
QRS duration at follow-up Day 7 Number Analyzed 15 participants 13 participants
84.4  (9.01) 88.6  (16.86)
Uncorrected QT interval on Day 1,Pre-dose Number Analyzed 5 participants 8 participants
350.0  (27.96) 357.5  (44.13)
Uncorrected QT interval on Day 3,12 hours Number Analyzed 13 participants 16 participants
357.8  (48.90) 369.8  (33.92)
Uncorrected QT interval at follow-up Day 7 Number Analyzed 15 participants 13 participants
354.3  (37.12) 377.5  (49.46)
Corrected QT interval(Basett) on Day 1,Pre-dose Number Analyzed 1 participants 4 participants
463.0 [1]   (NA) 469.4  (66.08)
Corrected QT interval(Basett) on Day 3,12 hours Number Analyzed 6 participants 6 participants
438.9  (13.02) 468.9  (41.59)
Corrected QT interval(Basett) at follow-up Day 7 Number Analyzed 7 participants 6 participants
453.5  (31.57) 483.5  (46.51)
Corrected QT interval(Fridericia), Day 1,Pre-dose Number Analyzed 1 participants 4 participants
423.4 [1]   (NA) 418.1  (49.03)
Corrected QT interval(Fridericia), Day 3,12 hours Number Analyzed 6 participants 6 participants
406.3  (20.18) 432.7  (35.92)
Corrected QT interval(Fridericia),follow-up Day 7 Number Analyzed 7 participants 6 participants
419.5  (12.66) 439.6  (36.29)
QTCU on Day 1,Pre-dose Number Analyzed 4 participants 4 participants
458.3  (8.81) 447.3  (27.65)
QTCU on Day 3,12 hours Number Analyzed 7 participants 10 participants
440.3  (40.07) 445.4  (28.11)
QTCU at follow-up Day 7 Number Analyzed 8 participants 7 participants
441.6  (17.72) 457.3  (26.12)
RR interval on Day 1,Pre-dose Number Analyzed 1 participants 4 participants
584.6 [1]   (NA) 513.6  (97.25)
RR interval on Day 3,12 hours Number Analyzed 6 participants 6 participants
638.8  (135.85) 623.2  (76.02)
RR interval at follow-up Day 7 Number Analyzed 7 participants 6 participants
661.7  (203.97) 582.9  (128.96)
[1]
Standard deviation could not be calculated as a single participant was analyzed.
4.Primary Outcome
Title Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)
Hide Description Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: giga per liter
Basophils on Day 1 at Pre-dose Number Analyzed 1 participants 3 participants
0.020 [1]   (NA) 0.000  (0.0000)
Basophils on Day 3 at 12 hours Number Analyzed 13 participants 15 participants
0.015  (0.0296) 0.011  (0.0277)
Basophils on Follow-up Day 7 Number Analyzed 9 participants 11 participants
0.025  (0.0431) 0.113  (0.1848)
Eosinophils on Day 1 at Pre-dose Number Analyzed 1 participants 3 participants
0.110 [1]   (NA) 0.233  (0.4041)
Eosinophils on Day 3 at 12 hours Number Analyzed 13 participants 15 participants
0.096  (0.1624) 0.163  (0.2280)
Eosinophils on Follow-up Day 7 Number Analyzed 9 participants 11 participants
0.137  (0.1074) 0.324  (0.4957)
Lymphocytes on Day 1 at Pre-dose Number Analyzed 2 participants 3 participants
4.81  (4.603) 0.52  (0.266)
Lymphocytes on Day 3 at 12 hours Number Analyzed 14 participants 15 participants
1.08  (0.948) 0.60  (0.380)
Lymphocytes on Follow-up Day 7 Number Analyzed 12 participants 11 participants
1.61  (1.244) 1.04  (0.663)
Monocytes on Day 1 at Pre-dose Number Analyzed 2 participants 3 participants
1.760  (1.7112) 0.377  (0.3356)
Monocytes on Day 3 at 12 hours Number Analyzed 14 participants 15 participants
0.503  (0.4046) 0.571  (0.6336)
Monocytes on Follow-up Day 7 Number Analyzed 11 participants 11 participants
0.669  (0.3986) 0.727  (0.5812)
Total neutrophils on Day 1 at Pre-dose Number Analyzed 2 participants 3 participants
6.990  (4.5113) 7.807  (9.3471)
Total neutrophils on Day 3 at 12 hours Number Analyzed 4 participants 15 participants
11.563  (6.0785) 9.931  (6.8583)
Total neutrophils on Follow-up Day 7 Number Analyzed 11 participants 11 participants
16.775  (21.6419) 11.761  (5.5496)
Platelet count on Day 1 at Pre-dose Number Analyzed 6 participants 4 participants
170.3  (67.26) 236.0  (158.73)
Platelet count on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
218.9  (120.68) 235.9  (134.43)
Platelet count on Follow-up Day 7 Number Analyzed 16 participants 14 participants
334.1  (169.06) 369.8  (169.70)
White blood cell count on Day 1 at Pre-dose Number Analyzed 6 participants 4 participants
15.15  (14.289) 10.72  (8.829)
White blood cell count on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
14.82  (5.927) 11.82  (6.618)
White blood cell count on Follow-up Day 7 Number Analyzed 16 participants 14 participants
14.09  (5.197) 36.56  (84.293)
[1]
Standard deviation was not calculated as a single participant was analyzed.
5.Primary Outcome
Title Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)
Hide Description Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: trillion cells per liter
Red blood cell count on Day 1 at Pre-dose Number Analyzed 6 participants 4 participants
3.207  (0.7733) 2.678  (0.5117)
Red blood cell count on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
3.271  (0.5725) 3.076  (0.5001)
Red blood cell count on Follow-up Day 7 Number Analyzed 16 participants 14 participants
3.352  (0.6374) 3.314  (0.7700)
Reticulocyte count on Day 1 at Pre-dose Number Analyzed 3 participants 1 participants
0.025  (0.0195) 0.044 [1]   (NA)
Reticulocyte count on Day 3 at 12 hours Number Analyzed 10 participants 12 participants
0.832  (2.5186) 3.697  (12.6920)
Reticulocyte count on Follow-up Day 7 Number Analyzed 11 participants 9 participants
1.607  (5.1055) 8.629  (25.6392)
[1]
Standard deviation was not calculated as a single participant was analyzed.
6.Primary Outcome
Title Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)
Hide Description Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: grams per liter
Hemoglobin on Day 1 at Pre-dose Number Analyzed 6 participants 4 participants
99.5  (24.83) 84.0  (13.09)
Hemoglobin on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
195.8  (286.77) 180.8  (266.16)
Hemoglobin on Follow-up Day 7 Number Analyzed 16 participants 14 participants
244.7  (401.03) 213.6  (301.50)
MCHC on Day 1 at Pre-dose Number Analyzed 6 participants 4 participants
331.8  (10.68) 339.5  (19.12)
MCHC on Day 3 at 12 hours Number Analyzed 17 participants 16 participants
328.4  (14.73) 330.8  (16.82)
MCHC on Follow-up Day 7 Number Analyzed 15 participants 11 participants
327.8  (12.35) 325.4  (6.82)
7.Primary Outcome
Title Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)
Hide Description Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: femtoliters
MCV on Day 1 at Pre-dose Number Analyzed 6 participants 3 participants
77.37  (33.654) 93.87  (0.971)
MCV on Day 3 at 12 hours Number Analyzed 18 participants 17 participants
91.28  (5.611) 90.69  (5.976)
MCV on Follow-up Day 7 Number Analyzed 16 participants 13 participants
92.53  (7.234) 90.46  (7.063)
8.Primary Outcome
Title Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)
Hide Description Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: picograms
MCH on Day 1 at Pre-dose Number Analyzed 3 participants 3 participants
30.30  (4.493) 30.40  (0.361)
MCH on Day 3 at 12 hours Number Analyzed 13 participants 11 participants
30.02  (2.695) 30.32  (1.955)
MCH on Follow-up Day 7 Number Analyzed 11 participants 8 participants
30.49  (2.545) 30.25  (2.071)
9.Primary Outcome
Title Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)
Hide Description Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: Fraction
Hematocrit on Day 1 at Pre-dose Number Analyzed 6 participants 4 participants
0.201  (0.1666) 0.196  (0.1333)
Hematocrit on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
0.271  (0.1071) 1.519  (5.3867)
Hematocrit on Follow-up Day 7 Number Analyzed 16 participants 14 participants
0.254  (0.1298) 2.270  (7.5504)
10.Primary Outcome
Title Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)
Hide Description Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: millimoles per liter
Calcium on Day 1 at Pre-dose Number Analyzed 3 participants 5 participants
1.927  (0.0736) 1.894  (0.1070)
Calcium on Day 3 at 12 hours Number Analyzed 11 participants 13 participants
1.983  (0.1220) 1.982  (0.1296)
Calcium on Follow-up Day 7 Number Analyzed 12 participants 11 participants
2.155  (0.1016) 2.104  (0.1448)
Chloride on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
108.8  (5.93) 104.0  (7.18)
Chloride on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
107.7  (5.12) 106.0  (6.05)
Chloride on Follow-up Day 7 Number Analyzed 16 participants 15 participants
104.4  (3.76) 103.7  (5.01)
Carbon dioxide on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
24.40  (5.273) 23.28  (6.685)
Carbon dioxide on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
26.35  (3.176) 27.83  (6.071)
Carbon dioxide on Follow-up Day 7 Number Analyzed 16 participants 15 participants
27.69  (3.728) 27.39  (3.412)
Glucose on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
6.015  (0.7499) 6.159  (1.1230)
Glucose on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
8.095  (2.1569) 7.411  (1.6158)
Glucose on Follow-up Day 7 Number Analyzed 15 participants 15 participants
6.701  (1.6354) 7.285  (1.5159)
Potassium on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
3.88  (0.444) 3.72  (0.164)
Potassium on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
4.20  (0.511) 3.96  (0.578)
Potassium on Follow-up Day 7 Number Analyzed 16 participants 15 participants
3.83  (0.505) 3.92  (0.435)
Sodium on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
141.8  (3.11) 137.6  (3.71)
Sodium on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
143.1  (4.46) 141.6  (4.03)
Sodium on Follow-up Day 7 Number Analyzed 16 participants 15 participants
141.9  (4.59) 139.7  (4.58)
Urea/Blood urea nitrogen on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
6.433  (3.0512) 11.399  (7.4163)
Urea/Blood urea nitrogen on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
10.410  (6.5542) 9.485  (6.5777)
Urea/Blood urea nitrogen on Follow-up Day 7 Number Analyzed 16 participants 15 participants
11.787  (9.3546) 9.207  (6.5375)
11.Primary Outcome
Title Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)
Hide Description Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: micromoles per liter
Direct bilirubin on Day 1 at Pre-dose Number Analyzed 4 participants 5 participants
10.663  (7.8146) 13.792  (17.7932)
Direct bilirubin on Day 3 at 12 hours Number Analyzed 15 participants 16 participants
10.446  (14.2406) 10.428  (22.4573)
Direct bilirubin on Follow-up Day 7 Number Analyzed 12 participants 11 participants
4.140  (3.5564) 2.576  (1.6103)
Total bilirubin on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
16.672  (11.1375) 21.926  (20.4768)
Total bilirubin on Day 3 at 12 hours Number Analyzed 17 participants 17 participants
16.803  (15.8462) 14.119  (24.8465)
Total bilirubin on Follow-up Day 7 Number Analyzed 14 participants 12 participants
12.547  (10.7837) 5.818  (3.0149)
Creatinine on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
85.194  (19.9261) 126.228  (71.9085)
Creatinine on Day 3 at 12 hours Number Analyzed 18 participants 18 participants
108.189  (102.4388) 103.066  (90.6252)
Creatinine on Follow-up Day 7 Number Analyzed 16 participants 15 participants
91.726  (45.2713) 90.516  (71.8052)
Uric acid on Day 1 at Pre-dose Number Analyzed 3 participants 3 participants
233.432  (67.9909) 181.453  (203.5924)
Uric acid on Day 3 at 12 hours Number Analyzed 13 participants 13 participants
192.925  (143.7971) 228.144  (134.9558)
Uric acid on Follow-up Day 7 Number Analyzed 12 participants 12 participants
241.766  (72.0137) 225.326  (144.4626)
12.Primary Outcome
Title Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)
Hide Description Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: International units per liter
Alkaline phosphatase on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
76.6  (18.57) 94.0  (50.86)
Alkaline phosphatase on Day 3 at 12 hours Number Analyzed 17 participants 17 participants
130.9  (68.16) 109.2  (63.02)
Alkaline phosphatase on Follow-up Day 7 Number Analyzed 14 participants 12 participants
101.1  (40.15) 117.0  (56.07)
Alanine amino transferase on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
101.8  (105.98) 56.8  (42.20)
Alanine amino transferase on Day 3 at 12 hours Number Analyzed 17 participants 17 participants
73.4  (71.27) 43.6  (50.72)
Alanine amino transferase on Follow-up Day 7 Number Analyzed 14 participants 12 participants
44.9  (42.74) 117.9  (224.94)
Asparatate amino transferase on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
96.8  (46.09) 64.6  (37.14)
Asparatate amino transferase on Day 3 at 12 hours Number Analyzed 17 participants 17 participants
56.2  (34.60) 62.0  (71.54)
Asparatate amino transferase on Follow-up Day 7 Number Analyzed 14 participants 12 participants
35.6  (20.25) 76.5  (106.39)
Gamma glutamyl transferase on Day 1 at Pre-dose Number Analyzed 2 participants 3 participants
96.0  (22.63) 40.7  (25.89)
Gamma glutamyl transferase on Day 3 at 12 hours Number Analyzed 13 participants 12 participants
156.5  (149.89) 98.4  (71.85)
Gamma glutamyl transferase on Follow-up Day 7 Number Analyzed 11 participants 12 participants
116.4  (105.36) 143.0  (138.22)
13.Primary Outcome
Title Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)
Hide Description Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: grams per liter
Albumin on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
25.6  (2.19) 18.6  (3.21)
Albumin on Day 3 at 12 hours Number Analyzed 17 participants 17 participants
25.5  (5.05) 22.3  (4.88)
Albumin on Follow-up Day 7 Number Analyzed 14 participants 12 participants
27.9  (6.62) 25.5  (6.27)
Total protein on Day 1 at Pre-dose Number Analyzed 5 participants 5 participants
54.60  (5.983) 50.20  (2.775)
Total protein on Day 3 at 12 hours Number Analyzed 16 participants 17 participants
55.06  (7.122) 52.12  (7.457)
Total protein on Follow-up Day 7 Number Analyzed 14 participants 11 participants
60.86  (8.646) 58.18  (10.323)
14.Primary Outcome
Title Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation 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 defined as 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part A Population was defined as all participants in Part A who received at least one dose of study medication.
Arm/Group Title Part A
Hide Arm/Group Description:
Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [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.
Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: Participants
Any AE 5
Anys SAE 3
15.Primary Outcome
Title Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)
Hide Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation 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 defined as 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects – Part B Population.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: Participant
Any AE 14 15
Any SAE 4 3
16.Secondary Outcome
Title Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)
Hide Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected 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). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic - Part A Population was defined as participants in the All Subjects – Part A population for whom a pharmacokinetic sample was obtained and analyzed and a result reported and received an active dose of GSK2586881.
Arm/Group Title Part A
Hide Arm/Group Description:
Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [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.
Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: nano grams per milliliter
GSK2586881 concentration at Pre-dose on Day 1 NA [1]   (NA)
GSK2586881 concentration at 5 minutes on Day 1 2854.0  (595.47)
GSK2586881 concentration at 10 minutes on Day 1 2692.8  (629.78)
GSK2586881 concentration at 2 hours on Day 1 2047.4  (497.19)
GSK2586881 concentration at 6 hours on Day 1 5460.0  (3213.96)
GSK2586881 concentration at 10 hours on Day 1 10276.6  (2641.49)
GSK2586881 concentration at 12 hours on Day 1 8265.4  (1905.29)
GSK2586881 concentration at 0 hours on Day 2 3621.6  (2654.21)
GSK2586881 concentration at 1 hour on Day 2 17558.6  (4359.04)
GSK2586881 concentration at 12 hours on Day 2 7237.8  (4281.27)
GSK2586881 concentration at 24 hours on Day 2 3517.8  (2433.49)
[1]
No concentration values detected for Pre-dose.
17.Secondary Outcome
Title Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)
Hide Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected 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). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic - Part B Population was defined as participants in the All Subjects – Part B population for whom a pharmacokinetic sample was obtained and analyzed and a result reported and received an active dose of GSK2586881. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter
GSK2586881 concentration at Pre-dose on Day 1 Number Analyzed 19 participants
NA [1]   (NA)
GSK2586881 concentration at 0.5 hours on Day 1 Number Analyzed 19 participants
5489.3  (1727.81)
GSK2586881 concentration at 2 hours on Day 1 Number Analyzed 18 participants
4334.0  (1880.42)
GSK2586881 concentration at 6 hours on Day 1 Number Analyzed 19 participants
5065.4  (8679.92)
GSK2586881 concentration at 12 hours on Day 1 Number Analyzed 17 participants
1815.9  (809.52)
GSK2586881 concentration at 0 hours on Day 2 Number Analyzed 18 participants
2115.3  (1164.12)
GSK2586881 concentration at 0 hours on Day 3 Number Analyzed 18 participants
2306.6  (1356.75)
GSK2586881 concentration at 0.5 hours on Day 3 Number Analyzed 18 participants
6810.4  (3135.66)
GSK2586881 concentration at 2 hours on Day 3 Number Analyzed 19 participants
6060.7  (2956.33)
GSK2586881 concentration at 6 hours on Day 3 Number Analyzed 17 participants
3808.9  (1953.82)
GSK2586881 concentration at 12 hours on Day 3 Number Analyzed 18 participants
2416.6  (1601.08)
GSK2586881 concentration at 18 hours on Day 3 Number Analyzed 16 participants
2701.6  (1874.28)
GSK2586881 concentration at 24 hours on Day 3 Number Analyzed 16 participants
2254.7  (1233.58)
[1]
No concentration values detected for Pre-dose.
18.Secondary Outcome
Title Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)
Hide Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic - Part A Population.
Arm/Group Title Part A
Hide Arm/Group Description:
Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [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.
Overall Number of Participants Analyzed 5
Geometric Mean (Standard Error)
Unit of Measure: liters per hour
0.384  (0.0886)
19.Secondary Outcome
Title Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)
Hide Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic - Part B Population.
Arm/Group Title Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 19
Geometric Mean (Standard Error)
Unit of Measure: liters per hour
0.698  (0.0608)
20.Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A)
Hide Description Renin-angiotensin system cascade biomarkers included Ang II and Ang (1-7). Blood samples for biomarker analyses were collected at 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 on Day 2.
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).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects – Part A Population
Arm/Group Title Part A
Hide Arm/Group Description:
Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [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.
Overall Number of Participants Analyzed 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: picograms per milliliter
AngII at Pre-dose on Day 1
26.5
(14.0 to 50.1)
AngII at 5 minutes on Day 1
7.7
(3.2 to 18.4)
AngII at 10 minutes on Day 1
6.2
(3.4 to 11.3)
AngII at 2 hours on Day 1
3.9
(0.9 to 17.4)
AngII at 6 hours on Day 1
4.3
(0.8 to 22.3)
AngII at 10 hours on Day 1
2.0
(0.4 to 10.3)
AngII at 12 hours on Day 1
3.3
(0.8 to 13.9)
AngII at 0 hours on Day 2
1.7
(0.2 to 13.3)
AngII at 1 hour on Day 2
4.3
(0.3 to 70.9)
AngII at 12 hours on Day 2
1.8
(0.2 to 15.5)
AngII at 24 hours on Day 2
1.5
(0.2 to 10.5)
Ang1-7 at Pre-dose on Day 1
4.3
(0.9 to 21.4)
Ang1-7 at 5 minutes on Day 1
28.7
(10.9 to 75.8)
Ang1-7 at 10 minutes on Day 1
25.7
(11.6 to 56.8)
Ang1-7 at 2 hours on Day 1
18.7
(6.4 to 54.1)
Ang1-7 at 6 hours on Day 1
22.8
(5.3 to 97.9)
Ang1-7 at 10 hours on Day 1
16.8
(1.2 to 243.5)
Ang1-7 at 12 hours on Day 1
15.1
(1.2 to 183.2)
Ang1-7 at 0 hours on Day 2
9.1
(0.6 to 130.1)
Ang1-7 at 1 hour on Day 2
20.9
(1.3 to 331.3)
Ang1-7 at 12 hours on Day 2
18.8
(2.6 to 138.4)
Ang1-7 at 24 hours on Day 2
5.2
(0.2 to 122.2)
21.Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A)
Hide Description Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours on Day 1 and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.
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).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects – Part A Population.
Arm/Group Title Part A
Hide Arm/Group Description:
Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [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.
Overall Number of Participants Analyzed 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
AngII/ Ang1-7 at Pre-dose on Day 1
6.167
(1.372 to 27.721)
AngII/ Ang1-7 at 5 minutes on Day 1
0.268
(0.099 to 0.722)
AngII/ Ang1-7 at 10 minutes on Day 1
0.241
(0.095 to 0.608)
AngII/ Ang1-7 at 2 hours on Day 1
0.210
(0.036 to 1.226)
AngII/ Ang1-7 at 6 hours on Day 1
0.190
(0.032 to 1.138)
AngII/ Ang1-7 at 10 hours on Day 1
0.118
(0.024 to 0.583)
AngII/ Ang1-7 at 12 hours on Day 1
0.221
(0.012 to 3.959)
AngII/ Ang1-7 at 0 hours on Day 2
0.182
(0.018 to 1.831)
AngII/ Ang1-7 at 1 hour on Day 2
0.206
(0.017 to 2.421)
AngII/ Ang1-7 at 12 hours on Day 2
0.094
(0.007 to 1.268)
AngII/ Ang1-7 at 24 hours on Day 2
0.290
(0.030 to 2.801)
22.Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B)
Hide Description Renin-angiotensin system cascade biomarkers included Ang II, Ang (1-7) and Ang (1-5). Blood samples for biomarker analyses were collected 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. Data has been presented for median along with the 95% credible interval.
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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Median (95% Confidence Interval)
Unit of Measure: picograms per milliliter
AngII at 0.5 hours Number Analyzed 16 participants 18 participants
14.14
(7.890 to 25.065)
2.44
(1.400 to 4.095)
AngII at 2 hours Number Analyzed 16 participants 16 participants
12.05
(6.658 to 21.146)
2.80
(1.585 to 4.735)
AngII at 6 hours Number Analyzed 16 participants 15 participants
11.00
(6.084 to 19.518)
2.89
(1.620 to 4.997)
AngII at 12 hours Number Analyzed 14 participants 15 participants
10.90
(5.920 to 19.824)
3.33
(1.853 to 5.727)
AngII at 24 hours Number Analyzed 14 participants 16 participants
8.35
(4.506 to 15.378)
2.41
(1.389 to 4.178)
AngII at 48 hours Number Analyzed 12 participants 18 participants
8.10
(4.219 to 15.071)
3.74
(2.232 to 6.677)
AngII at 48.5 hours Number Analyzed 13 participants 17 participants
8.63
(4.514 to 15.961)
2.89
(1.727 to 5.178)
AngII at 50 hours Number Analyzed 13 participants 17 participants
6.82
(3.551 to 12.510)
2.58
(1.534 to 4.570)
AngII at 54 hours Number Analyzed 14 participants 16 participants
7.03
(3.770 to 12.850)
2.32
(1.338 to 4.146)
AngII at 60 hours Number Analyzed 14 participants 16 participants
7.02
(3.883 to 12.768)
2.38
(1.374 to 4.179)
AngII at 66 hours Number Analyzed 14 participants 16 participants
7.33
(4.156 to 13.262)
1.84
(1.046 to 3.161)
AngII at 72 hours Number Analyzed 13 participants 14 participants
6.62
(3.701 to 12.174)
1.93
(1.067 to 3.441)
AngII at 96 hours Number Analyzed 9 participants 11 participants
4.72
(2.325 to 9.769)
1.70
(0.881 to 3.209)
AngII at 120 hours Number Analyzed 11 participants 10 participants
5.21
(3.036 to 10.126)
2.64
(1.437 to 5.586)
Ang1-5 at 0.5 hours Number Analyzed 15 participants 18 participants
2.17
(1.408 to 3.376)
8.58
(5.873 to 12.988)
Ang1-5 at 2 hours Number Analyzed 15 participants 16 participants
2.18
(1.410 to 3.383)
7.50
(5.124 to 11.367)
Ang1-5 at 6 hours Number Analyzed 15 participants 16 participants
2.34
(1.508 to 3.643)
8.38
(5.697 to 12.661)
Ang1-5 at 12 hours Number Analyzed 13 participants 16 participants
2.78
(1.784 to 4.363)
5.07
(3.370 to 7.533)
Ang1-5 at 24 hours Number Analyzed 13 participants 15 participants
2.38
(1.512 to 3.763)
3.57
(2.331 to 5.363)
Ang1-5 at 48 hours Number Analyzed 12 participants 17 participants
2.39
(1.519 to 3.724)
4.59
(3.030 to 6.854)
Ang1-5 at 48.5 hours Number Analyzed 13 participants 16 participants
2.30
(1.465 to 3.568)
5.26
(3.466 to 7.829)
Ang1-5 at 50 hours Number Analyzed 13 participants 16 participants
2.53
(1.619 to 3.924)
4.91
(3.213 to 7.268)
Ang1-5 at 54 hours Number Analyzed 14 participants 15 participants
2.52
(1.629 to 3.936)
3.21
(2.106 to 4.721)
Ang1-5 at 60 hours Number Analyzed 14 participants 15 participants
2.26
(1.478 to 3.490)
2.78
(1.868 to 4.143)
Ang1-5 at 66 hours Number Analyzed 15 participants 16 participants
2.19
(1.454 to 3.366)
2.71
(1.804 to 4.071)
Ang1-5 at 72 hours Number Analyzed 13 participants 14 participants
1.72
(1.125 to 2.662)
2.50
(1.640 to 3.884)
Ang1-5 at 96 hours Number Analyzed 9 participants 11 participants
2.23
(1.315 to 3.822)
1.28
(0.791 to 2.077)
Ang1-5 at 120 hours Number Analyzed 11 participants 10 participants
2.19
(1.451 to 3.412)
1.38
(0.868 to 2.403)
Ang1-7 at 0.5 hours Number Analyzed 16 participants 19 participants
3.12
(1.702 to 5.665)
13.15
(7.384 to 22.894)
Ang1-7 at 2 hours Number Analyzed 16 participants 16 participants
3.29
(1.786 to 5.965)
12.05
(6.774 to 21.245)
Ang1-7 at 6 hours Number Analyzed 16 participants 15 participants
2.92
(1.578 to 5.361)
15.33
(8.369 to 27.742)
Ang1-7 at 12 hours Number Analyzed 14 participants 16 participants
3.03
(1.607 to 5.711)
6.82
(3.800 to 12.383)
Ang1-7 at 24 hours Number Analyzed 14 participants 16 participants
2.87
(1.514 to 5.410)
6.25
(3.342 to 11.563)
Ang1-7 at 48 hours Number Analyzed 12 participants 18 participants
3.58
(1.878 to 6.875)
5.71
(3.154 to 9.797)
Ang1-7 at 48.5 hours Number Analyzed 13 participants 17 participants
2.77
(1.472 to 5.289)
5.54
(3.063 to 9.544)
Ang1-7 at 50 hours Number Analyzed 13 participants 17 participants
3.20
(1.696 to 6.064)
6.13
(3.399 to 10.648)
Ang1-7 at 54 hours Number Analyzed 14 participants 16 participants
3.16
(1.686 to 6.031)
5.78
(3.099 to 10.144)
Ang1-7 at 60 hours Number Analyzed 14 participants 16 participants
3.57
(1.907 to 6.701)
4.74
(2.542 to 8.631)
Ang1-7 at 66 hours Number Analyzed 15 participants 16 participants
3.40
(1.837 to 6.298)
3.97
(2.157 to 7.262)
Ang1-7 at 72 hours Number Analyzed 13 participants 14 participants
2.66
(1.389 to 5.051)
4.70
(2.510 to 8.532)
Ang1-7 at 96 hours Number Analyzed 9 participants 11 participants
1.77
(0.796 to 3.823)
2.43
(1.225 to 4.759)
Ang1-7 at 120 hours Number Analyzed 11 participants 10 participants
2.38
(1.213 to 4.155)
3.21
(1.857 to 6.147)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.083 to 0.359
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9999
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.111 to 0.492
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9997
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.121 to 0.568
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9997
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.136 to 0.660
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9991
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.133 to 0.632
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9631
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.213 to 1.081
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9941
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.33
Confidence Interval 95%
0.157 to 0.789
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9875
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.179 to 0.891
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9956
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.151 to 0.759
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9964
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.157 to 0.747
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9999
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.114 to 0.532
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9991
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.130 to 0.647
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9852
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.36
Confidence Interval (2-Sided) 0.9852%
0.137 to 0.906
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9719
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.230 to 1.014
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.98
Confidence Interval (2-Sided) 95%
2.263 to 6.919
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.46
Confidence Interval (2-Sided) 95%
1.976 to 6.052
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.59
Confidence Interval (2-Sided) 95%
2.060 to 6.345
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9806
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.82
Confidence Interval (2-Sided) 95%
1.031 to 3.170
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9129
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
0.828 to 2.636
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9891
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.92
Confidence Interval (2-Sided) 95%
1.098 to 3.349
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9983
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 2.29
Confidence Interval (2-Sided) 95%
1.316 to 3.974
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9900
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
1.112 to 3.359
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7996
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.729 to 2.163
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7778
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.718 to 2.087
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7730
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.705 to 2.113
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8951
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
0.814 to 2.604
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9324
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.276 to 1.183
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8982
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.351 to 1.257
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9998
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 4.22
Confidence Interval (2-Sided) 95%
1.910 to 8.905
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9993
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.67
Confidence Interval (2-Sided) 95%
1.689 to 7.970
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 5.26
Confidence Interval (2-Sided) 95%
2.392 to 11.754
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9713
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
0.972 to 5.136
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9649
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 2.19
Confidence Interval (2-Sided) 95%
0.940 to 4.975
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8749
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
0.711 to 3.473
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9566
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.99
Confidence Interval (2-Sided) 95%
0.899 to 4.342
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9549
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
0.862 to 4.173
Estimation Comments [Not Specified]
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9275
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
0.816 to 4.005
Estimation Comments [Not Specified]
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7483
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.584 to 3.007
Estimation Comments [Not Specified]
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6480
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.516 to 2.675
Estimation Comments [Not Specified]
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9038
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.76
Confidence Interval (2-Sided) 95%
0.741 to 4.170
Estimation Comments [Not Specified]
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7339
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.490 to 3.915
Estimation Comments [Not Specified]
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7714
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.651 to 3.321
Estimation Comments [Not Specified]
23.Secondary Outcome
Title 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)
Hide Description Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-5) and Ang II/Ang (1-7) and). Blood samples for biomarker analyses were collected 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. Data has been presented for median along with the 95% credible interval.
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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The All Subjects – Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Hide Arm/Group Description:
Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days.
Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Overall Number of Participants Analyzed 20 19
Median (95% Confidence Interval)
Unit of Measure: Ratio
Ang II/Ang1-5 at 0.5 hours Number Analyzed 16 participants 18 participants
4.35
(2.463 to 7.664)
0.29
(0.175 to 0.488)
Ang II/Ang1-5 at 2 hours Number Analyzed 16 participants 16 participants
3.82
(2.150 to 6.713)
0.38
(0.227 to 0.645)
Ang II/Ang1-5 at 6 hours Number Analyzed 16 participants 15 participants
3.20
(1.793 to 5.619)
0.36
(0.211 to 0.629)
Ang II/Ang1-5 at 12 hours Number Analyzed 14 participants 15 participants
2.90
(1.605 to 5.215)
0.72
(0.414 to 1.270)
Ang II/Ang1-5 at 24 hours Number Analyzed 14 participants 15 participants
2.35
(1.296 to 4.276)
0.68
(0.383 to 1.182)
Ang II/Ang1-5 at 48 hours Number Analyzed 13 participants 17 participants
2.68
(1.481 to 4.757)
0.85
(0.497 to 1.445)
Ang II/Ang1-5 at 48.5 hours Number Analyzed 14 participants 16 participants
2.90
(1.606 to 5.164)
0.56
(0.328 to 0.959)
Ang II/Ang1-5 at 50 hours Number Analyzed 14 participants 16 participants
2.11
(1.181 to 3.740)
0.53
(0.311 to 0.909)
Ang II/Ang1-5 at 54 hours Number Analyzed 15 participants 15 participants
2.21
(1.249 to 3.885)
0.68
(0.385 to 1.191)
Ang II/Ang1-5 at 60 hours Number Analyzed 15 participants 15 participants
2.52
(1.445 to 4.412)
0.86
(0.496 to 1.501)
Ang II/Ang1-5 at 66 hours Number Analyzed 15 participants 16 participants
2.90
(1.669 to 5.036)
0.64
(0.370 to 1.105)
Ang II/Ang1-5 at 72 hours Number Analyzed 14 participants 14 participants
2.91
(1.620 to 5.153)
0.76
(0.429 to 1.335)
Ang II/Ang1-5 at 96 hours Number Analyzed 10 participants 11 participants
1.72
(0.870 to 3.387)
1.41
(0.738 to 2.695)
Ang II/Ang1-5 at 120 hours Number Analyzed 12 participants 10 participants
1.93
(1.058 to 3.508)
1.53
(0.768 to 2.872)
Ang II/Ang1-7 at 0.5 hours Number Analyzed 17 participants 18 participants
3.10
(1.681 to 5.669)
0.19
(0.110 to 0.342)
Ang II/Ang1-7 at 2 hours Number Analyzed 17 participants 16 participants
2.52
(1.379 to 4.611)
0.24
(0.135 to 0.432)
Ang II/Ang1-7 at 6 hours Number Analyzed 17 participants 14 participants
2.63
(1.456 to 4.767)
0.20
(0.109 to 0.378)
Ang II/Ang1-7 at 12 hours Number Analyzed 15 participants 15 participants
2.50
(1.352 to 4.675)
0.49
(0.267 to 0.913)
Ang II/Ang1-7 at 24 hours Number Analyzed 15 participants 16 participants
2.11
(1.127 to 3.990)
0.37
(0.200 to 0.671)
Ang II/Ang1-7 at 48 hours Number Analyzed 13 participants 18 participants
1.61
(0.843 to 3.105)
0.65
(0.363 to 1.146)
Ang II/Ang1-7 at 48.5 hours Number Analyzed 14 participants 17 participants
2.18
(1.147 to 4.165)
0.51
(0.291 to 0.917)
Ang II/Ang1-7 at 50 hours Number Analyzed 14 participants 17 participants
1.51
(0.799 to 2.887)
0.42
(0.233 to 0.747)
Row 23Ang II/Ang1-7 at 54 hours Number Analyzed 15 participants 16 participants
1.64
(0.872 to 3.105)
0.40
(0.213 to 0.719)
Ang II/Ang1-7 at 60 hours Number Analyzed 15 participants 16 participants
1.55
(0.817 to 2.945)
0.48
(0.264 to 0.878)
Ang II/Ang1-7 at 66 hours Number Analyzed 15 participants 16 participants
1.81
(0.964 to 3.354)
0.45
(0.246 to 0.825)
Ang II/Ang1-7 at 72 hours Number Analyzed 14 participants 14 participants
1.75
(0.931 to 3.295)
0.42
(0.219 to 0.796)
Ang II/Ang1-7 at 96 hours Number Analyzed 10 participants 11 participants
2.02
(0.951 to 4.323)
0.69
(0.335 to 1.406)
Ang II/Ang1-7 at 120 hours Number Analyzed 12 participants 10 participants
1.66
(0.826 to 3.178)
0.64
(0.311 to 1.568)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.032 to 0.140
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.048 to 0.209
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.054 to 0.243
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9996
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.113 to 0.547
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9991
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.130 to 0.634
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9979
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.149 to 0.682
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.19
Confidence Interval 95%
0.091 to 0.417
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9998
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.119 to 0.539
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9985
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.141 to 0.666
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9977
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.162 to 0.730
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9999
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.105 to 0.468
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9996
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.119 to 0.570
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6621
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.319 to 2.136
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7085
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.324 to 1.847
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
0.028 to 0.140
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.043 to 0.216
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0.034 to 0.177
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9998
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.086 to 0.453
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9999
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.075 to 0.400
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9863
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.173 to 0.901
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9998
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.103 to 0.529
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9992
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.119 to 0.626
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9995
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.102 to 0.561
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9964
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.131 to 0.729
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9995
Comments [Not Specified]
Method Bayesian repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.107 to 0.584
Estimation Comments [Not Specified]
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Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9993
Comments [Not Specified]
Method Ratio of Active/Placebo
Comments [Not Specified]