Trial Outcomes & Findings for GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults (NCT NCT00089986)

Last Updated: 2017-08-21

Results Overview

Mortality was assessed by the number of participants who died between days 1 and 28. A summary of death details was given which included whether the participant died between days 1 and 28, whether the death was related sepsis, cause of death, the source of the information, and whether the cause of death was verified by a death record. Participants who had withdrawn from study and all study assessments and for whom survival at day 28 could not be confirmed was treated as deaths for the primary endpoint. The difference in all-cause 28-day mortality rates for each treatment group versus the placebo group in the ITT Population was calculated as placebo - treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

1415 participants

Primary outcome timeframe

Day 1 (post-infusion) up to Day 28 Follow-up

Results posted on

2017-08-21

Participant Flow

The study was planned on 1845 participants, hospitalized with suspected or confirmed gram-negative severe sepsis, male or female \>=18 years of age at 235 centers across 31 countries from 02 September 2004 to 25 June 2007.

A total of 1415 participant numbers were assigned during randomization process, five were duplicate randomization numbers and for other two, the participants did not provide informed consent, precluding them from enrollment. Out of 1408 participants, 29 did not receive study medication, remaining 1379 included in Intent-to-Treat (ITT) Population.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, intravenously (IV) as a loading dose infused over 2 hours (h) followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 milliliters per kilogram per hour (mL/kg/h) for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 milligrams per milliliter (mg/mL) lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 milligram (mg)/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Overall Study STARTED	599	598	182
Overall Study COMPLETED	584	574	172
Overall Study NOT COMPLETED	15	24	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, intravenously (IV) as a loading dose infused over 2 hours (h) followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 milliliters per kilogram per hour (mL/kg/h) for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 milligrams per milliliter (mg/mL) lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 milligram (mg)/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Overall Study Adverse Event	6	9	6
Overall Study Lost to Follow-up	3	1	1
Overall Study Protocol Violation	0	1	0
Overall Study Patient transferred to another hospital	2	1	0
Overall Study Subject withdrew but agreed follow up	1	2	0
Overall Study Hemohlobin stopping rule	0	1	0
Overall Study Investigator decision to withdrew	0	1	0
Overall Study Enrollment in another study	0	1	0
Overall Study Family decision	0	1	0
Overall Study Do not resuscitate (DNR)	0	0	1
Overall Study Withdrawal by Subject	3	6	2

Baseline Characteristics

GR270773 In The Treatment Of Suspected Or Confirmed Gram-Negative Severe Sepsis In Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=599 Participants Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 n=598 Participants Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 n=182 Participants Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.	Total n=1379 Participants Total of all reporting groups
Age, Continuous	63.1 Years STANDARD_DEVIATION 16.41 • n=5 Participants	62.8 Years STANDARD_DEVIATION 16.27 • n=7 Participants	64.8 Years STANDARD_DEVIATION 15.47 • n=5 Participants	63.2 Years STANDARD_DEVIATION 16.23 • n=4 Participants
Sex: Female, Male Female	254 Participants n=5 Participants	239 Participants n=7 Participants	80 Participants n=5 Participants	573 Participants n=4 Participants
Sex: Female, Male Male	345 Participants n=5 Participants	359 Participants n=7 Participants	102 Participants n=5 Participants	806 Participants n=4 Participants
Race/Ethnicity, Customized Arabic/North African	7 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Black	16 Participants n=5 Participants	14 Participants n=7 Participants	2 Participants n=5 Participants	32 Participants n=4 Participants
Race/Ethnicity, Customized East & South East Asian	51 Participants n=5 Participants	44 Participants n=7 Participants	14 Participants n=5 Participants	109 Participants n=4 Participants
Race/Ethnicity, Customized Japanese	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized South Asian	29 Participants n=5 Participants	32 Participants n=7 Participants	2 Participants n=5 Participants	63 Participants n=4 Participants
Race/Ethnicity, Customized White/Caucasian	484 Participants n=5 Participants	494 Participants n=7 Participants	161 Participants n=5 Participants	1139 Participants n=4 Participants
Race/Ethnicity, Customized Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized American Indian	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Missing	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (post-infusion) up to Day 28 Follow-up

Population: ITT Population was defined as all randomized participants from all three stages who receive any study drug.

Outcome measures

Outcome measures
Measure	Placebo n=599 Participants Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 n=598 Participants Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 n=182 Participants Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Percentage of Participants With 28-Day All Cause Mortality	26.9 Percentage of participants	25.8 Percentage of participants	31.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-infusion) up to Day 28 Follow-up

Population: ITT Population. Organ failure occurring during the 28 days post-enrollment that was not in failure at enrollment. Subjects who die prior to observing a new organ failure are counted as a failure.

The new onset organ failure was defined as first time each of the following criteria were met after start of study medication up to Day 28. Respiratory failure: defined by requiring mechanical ventilation not less than 24 hours due to surgery. Renal failure: defined by requiring the initiation of hemodialysis or hemofiltration. Coagulopathy: defined by disseminated intravascular coagulation (DIC) requiring transfusion with platelets or fresh frozen plasma or anticoagulant therapy. Cardiovascular failure: defined by sustained hypotension requiring vasopressor support of dopamine \>5 microgram per kilogram per minute (µg/kg/min), epinephrine, norepinephrine, phenylephrine or vasopressin at any dose if used to increase blood pressure for \>=6 continuous h. Analysis was done treating the death as a new onset organ failure (counted in both the numerator and denominator).

Outcome measures

Outcome measures
Measure	Placebo n=599 Participants Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 n=598 Participants Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 n=182 Participants Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Number of Participants With New Onset Organ Failure, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrolment	122 Participants	157 Participants	57 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-infusion) up to Day 28 Follow up

Population: ITT Population. Organ failure occurring during the 28 days post-enrollment that was not in failure at enrollment. Participants who died prior to observing a new failure are excluded from analysis.

Respiratory failure: defined by requiring mechanical ventilation not less than 24 hours due to surgery. Renal failure: defined by requiring the initiation of hemodialysis or hemofiltration. Coagulopathy: defined by disseminated intravascular coagulation (DIC) requiring transfusion with platelets or fresh frozen plasma or anticoagulant therapy. Cardiovascular failure: defined by sustained hypotension requiring vasopressor support of dopamine \>5 microgram per kilogram per minute (µg/kg/min), epinephrine, norepinephrine, phenylephrine or vasopressin at any dose if used to increase blood pressure for \>=6 continuous h. For each organ failure type and the number of new onset organ failures per participants for each organ failure type, the denominator only included participants who did not have that type of organ failure at Baseline. At Baseline a participant could enter the study with a type of organ failure, that type of failure was not reported as a new onset organ failure.

Outcome measures

Outcome measures
Measure	Placebo n=599 Participants Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 n=598 Participants Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 n=182 Participants Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment Respiratory failure, n= 297, 333, 99	50 Participants	61 Participants	23 Participants
Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment Cardiovascular failure, n= 150, 161, 43	33 Participants	48 Participants	15 Participants
Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment Renal failure, n= 460, 474, 138	40 Participants	47 Participants	22 Participants
Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment Coagulopathy, n= 344, 355, 107	36 Participants	41 Participants	16 Participants

SECONDARY outcome

Timeframe: Day 1 (pre-infusion) up to Day 28 Follow-up

Population: ITT Population.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition or common toxicity criteria (CTC) grade 4 laboratory abnormalities of national cancer institute not associated with the underlying sepsis unless more severe than expected for the participants condition.

Outcome measures

Outcome measures
Measure	Placebo n=599 Participants Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 n=598 Participants Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 n=182 Participants Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Assessment of Safety/Tolerability by Determining the Number of Participants With Any Adverse Events (AE), Serious Adverse Events (SAE) and Fatal SAE Any AE	423 Participants	442 Participants	144 Participants
Assessment of Safety/Tolerability by Determining the Number of Participants With Any Adverse Events (AE), Serious Adverse Events (SAE) and Fatal SAE Any SAE	213 Participants	235 Participants	77 Participants
Assessment of Safety/Tolerability by Determining the Number of Participants With Any Adverse Events (AE), Serious Adverse Events (SAE) and Fatal SAE Any fatal SAE	85 Participants	70 Participants	33 Participants

Adverse Events

Placebo

Serious events: 213 serious events

Other events: 160 other events

Deaths: 85 deaths

Low GR270773

Serious events: 235 serious events

Other events: 183 other events

Deaths: 70 deaths

High GR270773

Serious events: 77 serious events

Other events: 60 other events

Deaths: 33 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=599 participants at risk Eligible participants were administered matching placebo to low-dose GR270773 or high-dose GR270773, IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The low placebo rate consisted of a loading dose of 0.75 mL/kg/h for 2 h and a maintenance dose of 0.1 mL/kg/h for 70 h. The high placebo rate consisted of a loading dose of 1.5 mL/kg/h for 2 h and a maintenance dose of 0.15 mL/kg/h for 70 h.	Low GR270773 n=598 participants at risk Eligible participants were administered low-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The low dose emulsion consisted of a loading dose of 75 mg/kg/h which was equivalent to 0.75 mL/kg/h for 2 h and a maintenance dose of 10 mg/kg/h which was equivalent to 0.1 mL/kg/h for 70 h. The total dose was 850 mg/kg.	High GR270773 n=182 participants at risk Eligible participants were administered high-dose GR270773 IV as a loading dose infused over 2 h followed by a maintenance dose administered as a continuous infusion for 70 h, for a total treatment period of 72 h. The study medication was administered as a sterile 100 mg/mL lipid emulsion for IV administration. The high dose emulsion consisted of a loading dose of 15 mg/kg/h which was equivalent to 1.5 mL/kg/h for 2 h and a maintenance dose of 15 mg/kg/h which was equivalent to 0.15 mL/kg/h for 70 h. The total dose was 1350 mg/kg.
Blood and lymphatic system disorders Anaemia	12.7% 76/599 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	14.5% 87/598 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	15.4% 28/182 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.
Gastrointestinal disorders Diarrhoea	5.5% 33/599 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	8.4% 50/598 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	15.4% 28/182 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.
Gastrointestinal disorders Nausea	4.2% 25/599 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	5.2% 31/598 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	8.2% 15/182 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.
Metabolism and nutrition disorders Hypokalaemia	8.5% 51/599 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	8.9% 53/598 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	8.8% 16/182 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.
Cardiac disorders Atrial fibrillation	7.3% 44/599 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	6.9% 41/598 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.	5.5% 10/182 • AE and SAE were collected from Baseline (Day 1, pre-infusion) to Day 28 Follow-up ITT Population was used which was defined as all randomized participants from all three stages who receive any study drug.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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