Trial Outcomes & Findings for A Study With SAGE-547 for Super-Refractory Status Epilepticus (NCT NCT02477618)

Last Updated: 2025-10-14

Results Overview

Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression electroencephalogram (EEG) pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG. A responder was a participant who was able to be weaned off all third-line agents prior to the end of the SAGE-547 or placebo infusion and remain off all third-line agents for \>=24 hours after the end of the study drug infusion. The primary analysis was a comparison between SAGE-547 and placebo of the proportion of responders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

132 participants

Primary outcome timeframe

7 days

Results posted on

2025-10-14

Participant Flow

Participants took part in the study at 122 investigative sites in Canada, United States, Austria, Denmark, Estonia, Finland, France, Germany, Israel, Italy, Serbia, Spain and United Kingdom from 31 July 2015 to 11 August 2017.

Participants 2 years of age and older with Super-Refractory Status Epilepticus were eligible. One participant in the placebo group was erroneously given SAGE-547 and was, therefore, included in the SAGE- 547 group.

Participant milestones

Participant milestones
Measure	Placebo Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Study STARTED	65	67
Overall Study Intent-to-Treat Analysis Set	66	66
Overall Study COMPLETED	50	53
Overall Study NOT COMPLETED	15	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Study Completed Visits but Discontinued Drug	2	1
Overall Study Died in Double-Blind Treatment Period	11	11
Overall Study Adverse Event	1	1
Overall Study Transferred Away from Study Site	1	0
Overall Study Left Study Site for Rehabilitation	0	1

Baseline Characteristics

A Study With SAGE-547 for Super-Refractory Status Epilepticus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=65 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=67 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.	Total n=132 Participants Total of all reporting groups
Age, Continuous	37.8 years STANDARD_DEVIATION 22.69 • n=5 Participants	41.3 years STANDARD_DEVIATION 23.89 • n=7 Participants	39.6 years STANDARD_DEVIATION 23.29 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	35 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Race/Ethnicity, Customized White	47 Participants n=5 Participants	45 Participants n=7 Participants	92 Participants n=5 Participants
Race/Ethnicity, Customized Black	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	55 Participants n=5 Participants	61 Participants n=7 Participants	116 Participants n=5 Participants

PRIMARY outcome

Timeframe: 7 days

Population: The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Number of Participants Able to be Weaned Off All Third-Line Agents Prior to End of Double-Blind SAGE-547 or Placebo Infusion, and Remain Off All Third-Line Agents for ≥ 24 Hours Following the End of SAGE-547 or Placebo Infusion	28 Participants	29 Participants

SECONDARY outcome

Timeframe: Up to 21 days

Population: The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, overall number of participants analyzed (N) indicates participants analyzed for this outcome measure.

Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG. A responder was a participant who was able to be weaned off all third-line agents prior to the end of the SAGE-547 or placebo infusion and remain off all third-line agents for \>=24 hours after the end of the study drug infusion. The primary analysis was a comparison between SAGE-547 and placebo of the proportion of responders.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=29 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression	13.500 days Interval 0.06 to 18.0	14.000 days Interval 0.18 to 16.0

SECONDARY outcome

Timeframe: Day 6

Population: The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion	45 Participants	38 Participants

SECONDARY outcome

Timeframe: Up to 21 days

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=38 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression	7.000 days Interval 0.0 to 20.0	15.000 days Interval 0.0 to 19.0

SECONDARY outcome

Timeframe: Up to 21 days

Population: The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, number of participants analyzed (N) indicates participants with available data at each time point for this outcome measure.

The CGI scale was used to integrate several sources of information into a single rating of a participant's condition. The CGI was rated on a 7-point scale, from a minimum of 0 to a maximum of 7, where 0 = Not assessed; 1 = Normal, not at all ill; 2 = Borderline physically ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill participants. A negative change from baseline indicates improvement. A positive change from baseline indicates worsening. Here, study visits followed by "R" indicate the Open-label Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Change in Clinical Global Impression Scale (CGI) Baseline	6.0 units on scale Standard Deviation 0.89	5.9 units on scale Standard Deviation 1.31
Change in Clinical Global Impression Scale (CGI) Visit 12	-1.0 units on scale Standard Deviation 1.42	-0.6 units on scale Standard Deviation 1.91
Change in Clinical Global Impression Scale (CGI) Visit 12R	-0.7 units on scale Standard Deviation 1.36	-0.5 units on scale Standard Deviation 1.19

SECONDARY outcome

Timeframe: Up to 21 days

Here, study visits followed by "R" indicate the Open-label Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12 Visit 12	10.05 days Standard Deviation 6.738	11.15 days Standard Deviation 6.058
Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12 Visit 12R	11.08 days Standard Deviation 6.557	9.23 days Standard Deviation 6.345

SECONDARY outcome

Timeframe: Up to 21 days

Here, study visits followed by "R" indicate the Open-label Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12 Visit 12	8.22 days Standard Deviation 7.289	7.50 days Standard Deviation 6.626
Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12 Visit 12R	7.52 days Standard Deviation 7.054	6.08 days Standard Deviation 5.932

SECONDARY outcome

Timeframe: Up to 21 days

Here, study visits followed by "R" indicate the Open-label Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Number of Separate Episodes of Status Epilepticus Up to Visit 12 Visit 12	1.3 episodes Standard Deviation 0.50	1.4 episodes Standard Deviation 0.55
Number of Separate Episodes of Status Epilepticus Up to Visit 12 Visit 12R	2.2 episodes Standard Deviation 2.17	1.0 episodes Standard Deviation 0.00

SECONDARY outcome

Timeframe: Up to 21 days

Here, study visits followed by "R" indicate the Open-label Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=66 Participants SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Number of Participants With a New Diagnosis of Epilepsy After Visit 11 Visit 12	0 Participants	5 Participants
Number of Participants With a New Diagnosis of Epilepsy After Visit 11 Visit 12R	5 Participants	3 Participants

Adverse Events

Placebo

Serious events: 22 serious events

Other events: 58 other events

Deaths: 12 deaths

SAGE-547

Serious events: 27 serious events

Other events: 60 other events

Deaths: 17 deaths

Serious adverse events

Other adverse events

Additional Information

Helen Colquhoun, MD - Vice President, Medical Science

Sage Therapeutics

Phone: (617) 229-5234

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=65 participants at risk Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.	SAGE-547 n=67 participants at risk SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Blood and lymphatic system disorders Anaemia	10.8% 7/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	17.9% 12/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Blood and lymphatic system disorders Leukocytosis	4.6% 3/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Blood and lymphatic system disorders Thrombocytopenia	10.8% 7/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Cardiac disorders Tachycardia	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	11.9% 8/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Cardiac disorders Atrial fibrillation	3.1% 2/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Cardiac disorders Sinus tachycardia	0.00% 0/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Gastrointestinal disorders Diarrhoea	10.8% 7/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	17.9% 12/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Gastrointestinal disorders Constipation	12.3% 8/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	14.9% 10/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Gastrointestinal disorders Vomiting	3.1% 2/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Gastrointestinal disorders Abdominal distension	0.00% 0/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
General disorders Pyrexia	32.3% 21/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	28.4% 19/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
General disorders Hyperthermia	1.5% 1/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
General disorders Peripheral swelling	0.00% 0/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
General disorders Oedema	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
General disorders Hypothermia	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	1.5% 1/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Infections and infestations Urinary tract infection	21.5% 14/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	19.4% 13/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Infections and infestations Pneumonia	16.9% 11/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	19.4% 13/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Infections and infestations Fungal infection	1.5% 1/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Infections and infestations Sepsis	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Investigations Aspartate aminotransferase increased	9.2% 6/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Investigations Lipase increased	9.2% 6/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Investigations Alanine aminotransferase increased	7.7% 5/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Investigations Blood potassium decreased	1.5% 1/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Investigations White blood cell count increased	0.00% 0/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Investigations Electrocardiogram QT prolonged	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hypokalaemia	16.9% 11/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	14.9% 10/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hypophosphataemia	9.2% 6/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	11.9% 8/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Metabolic acidosis	3.1% 2/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	11.9% 8/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hypernatraemia	9.2% 6/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	9.0% 6/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hyponatraemia	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hyperglycaemia	1.5% 1/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hyperammonaemia	0.00% 0/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Fluid overload	3.1% 2/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Metabolism and nutrition disorders Hypocalcaemia	10.8% 7/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Psychiatric disorders Agitation	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Renal and urinary disorders Haematuria	1.5% 1/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Respiratory, thoracic and mediastinal disorders Pleural effusion	12.3% 8/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	20.9% 14/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Respiratory, thoracic and mediastinal disorders Atelectasis	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Skin and subcutaneous tissue disorders Decubitus ulcer	12.3% 8/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	7.5% 5/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Skin and subcutaneous tissue disorders Erythema	3.1% 2/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Skin and subcutaneous tissue disorders Rash	3.1% 2/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	6.0% 4/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Vascular disorders Hypertension	9.2% 6/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	11.9% 8/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Vascular disorders Hypotension	15.4% 10/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	9.0% 6/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
Vascular disorders Deep vein thrombosis	6.2% 4/65 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.	4.5% 3/67 • Up to approximately 27 days The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.