Trial Outcomes & Findings for Safety, Efficacy and Pharmacokinetics of CF-301 vs. Placebo in Addition to Antibacterial Therapy for Treatment of S. Aureus Bacteremia (NCT NCT03163446)

NCT ID: NCT03163446

Last Updated: 2021-10-08

Results Overview

Number and percentage of patients with treatment-emergent adverse events (TEAEs)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

121 participants

Primary outcome timeframe

Through Day 7, at Test of Cure (TOC) between 56-70 days, and at Day 180

Results posted on

2021-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	CF-301 Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Overall Study STARTED	73	48
Overall Study COMPLETED	45	31
Overall Study NOT COMPLETED	28	17

Reasons for withdrawal

Reasons for withdrawal
Measure	CF-301 Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Overall Study Unable to return for Day 180 visit	2	0
Overall Study Withdrawal by Subject	2	6
Overall Study Death	16	5
Overall Study Lost to Follow-up	6	5
Overall Study Physician Decision	1	1
Overall Study Patient randomized but went to surgery and was unable to be dosed.	1	0

Baseline Characteristics

Safety, Efficacy and Pharmacokinetics of CF-301 vs. Placebo in Addition to Antibacterial Therapy for Treatment of S. Aureus Bacteremia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CF-301 n=73 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=48 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Total n=121 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	50 Participants n=5 Participants	36 Participants n=7 Participants	86 Participants n=5 Participants
Age, Categorical >=65 years	23 Participants n=5 Participants	12 Participants n=7 Participants	35 Participants n=5 Participants
Age, Continuous	56.6 years STANDARD_DEVIATION 15.24 • n=5 Participants	55.0 years STANDARD_DEVIATION 15.62 • n=7 Participants	55.9 years STANDARD_DEVIATION 15.39 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	16 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	32 Participants n=7 Participants	82 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	51 Participants n=5 Participants	30 Participants n=7 Participants	81 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	58 participants n=5 Participants	38 participants n=7 Participants	96 participants n=5 Participants
Region of Enrollment United Kingdom	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Russia	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Greece	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Guatemala	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Italy	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Israel	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Chile	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment France	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Germany	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Diagnosis Right-sided endocarditis	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Diagnosis Left-sided endocarditis	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Diagnosis Right and left-sided endocarditis	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Diagnosis Uncomplicated bloodstream infection (BSI)	13 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants
Diagnosis Complicated bloodstream infection (BSI)	43 Participants n=5 Participants	37 Participants n=7 Participants	80 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through Day 7, at Test of Cure (TOC) between 56-70 days, and at Day 180

Population: Safety population

Number and percentage of patients with treatment-emergent adverse events (TEAEs)

Outcome measures

Outcome measures
Measure	CF-301 n=72 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=47 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Incidence of Adverse Events [Safety and Tolerability] TEAE through Day 7	48 Participants	30 Participants
Incidence of Adverse Events [Safety and Tolerability] TEAE through TOC	64 Participants	40 Participants
Incidence of Adverse Events [Safety and Tolerability] TEAE through Day 180	67 Participants	40 Participants

PRIMARY outcome

Timeframe: Day 14

Population: Microbiological Intent-to-Treat (mITT) population

Description of clinical outcome in the Microbiological Intent-to-Treat (mITT) population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clinical Outcome at Day 14 Non-response	18 Participants	13 Participants
Clinical Outcome at Day 14 Indeterminate	3 Participants	5 Participants
Clinical Outcome at Day 14 Responder (Improvement/Response)	50 Participants	27 Participants

PRIMARY outcome

Timeframe: Pre-dose and at 0.5, 1.5, 2, 2.25, 3, 4, 8, 14, 24, and 48 hours after the start of CF-301 infusion

Population: PK Population (patients with serial PK samples)

CF-301 plasma concentrations at specified timepoints.

Outcome measures

Outcome measures
Measure	CF-301 n=13 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
CF-301 Maximum Plasma Concentration (Cmax)	1450.33 ng/mL Standard Deviation 636.83	—

PRIMARY outcome

Timeframe: Pre-dose and at 0.5, 1.5, 2, 2.25, 3, 4, 8, 14, 24, and 48 hours after the start of CF-301 infusion

Population: PK Population (patients with serial PK samples)

CF-301 plasma concentrations at specified time points

Outcome measures

Outcome measures
Measure	CF-301 n=13 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
CF-301 Area Under the Curve (AUC 0-t)	5667.42 ng*hr/mL Standard Deviation 3032.03	—

SECONDARY outcome

Timeframe: Day 7

Population: mITT population

Description of clinical outcome in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clinical Outcome at Day 7 Responder (Improvement/Response)	51 Participants	31 Participants
Clinical Outcome at Day 7 Non-response	17 Participants	11 Participants
Clinical Outcome at Day 7 Indeterminate	3 Participants	3 Participants

SECONDARY outcome

Timeframe: EOT between 28-42 days

Population: mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clinical Outcome at End of Standard of Care Antibacterial Therapy (EOT) Responder (Improvement/Response)	44 Participants	28 Participants
Clinical Outcome at End of Standard of Care Antibacterial Therapy (EOT) Non-response	22 Participants	13 Participants
Clinical Outcome at End of Standard of Care Antibacterial Therapy (EOT) Indeterminate	5 Participants	4 Participants

SECONDARY outcome

Timeframe: TOC between 56-70 days

Population: mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clinical Outcome at Test of Cure (TOC) Responder (Improvement/Response)	39 Participants	24 Participants
Clinical Outcome at Test of Cure (TOC) Non-Response	25 Participants	15 Participants
Clinical Outcome at Test of Cure (TOC) Indeterminate	7 Participants	6 Participants

SECONDARY outcome

Timeframe: Day 7

Population: mITT population

Number and percentage of patients with clearance of bacteremia in the mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration Clearance/presumed clearance of bacteremia	59 Participants	39 Participants
Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration Ongoing bacteremia	7 Participants	2 Participants
Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration Indeterminate	2 Participants	2 Participants
Clearance of Bacteremia at Day 7 After CF-301/Placebo Administration Presumed ongoing bacteremia	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 14

Population: mITT population

Number and percentage of patients with clearance of bacteremia in the mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration Clearance/presumed clearance of bacteremia	64 Participants	38 Participants
Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration Ongoing bacteremia	4 Participants	2 Participants
Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration Presumed ongoing bacteremia	2 Participants	3 Participants
Clearance of Bacteremia at Day 14 After CF-301/Placebo Administration Indeterminate	1 Participants	2 Participants

SECONDARY outcome

Timeframe: EOT between 28-42 days

Population: mITT population

Number and percentage of patients with microbiological eradication in the mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT) Eradication/presumptive eradication	50 Participants	31 Participants
Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT) Persistence	0 Participants	2 Participants
Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT) Presumed persistence	16 Participants	8 Participants
Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT) Relapse	0 Participants	0 Participants
Microbiological Eradication at End of Standard of Care Antibacterial Therapy (EOT) Indeterminate	5 Participants	4 Participants

SECONDARY outcome

Timeframe: TOC between 56-70 days

Population: mITT population

Number and percentage of patients with microbiological eradication in the mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=71 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=45 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Microbiological Eradication at Test of Cure (TOC) Eradication/presumptive eradication	46 Participants	31 Participants
Microbiological Eradication at Test of Cure (TOC) Persistence	0 Participants	0 Participants
Microbiological Eradication at Test of Cure (TOC) Presumed persistence	18 Participants	9 Participants
Microbiological Eradication at Test of Cure (TOC) Relapse	0 Participants	0 Participants
Microbiological Eradication at Test of Cure (TOC) Indeterminate	7 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 14

Population: Microbiological Intent-to-Treat (mITT) population

Description of clinical outcome in the MRSA subgroup in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.

Outcome measures

Outcome measures
Measure	CF-301 n=27 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=16 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clinical Outcome at Day 14 in MRSA Subgroup Indeterminate	3 Participants	3 Participants
Clinical Outcome at Day 14 in MRSA Subgroup Responder (Improvement/Response)	20 Participants	5 Participants
Clinical Outcome at Day 14 in MRSA Subgroup Non-response	4 Participants	8 Participants

POST_HOC outcome

Timeframe: Day 14

Population: mITT population

Description of clinical responder at Day 14 in patients with complicated bloodstream infection (cBSI) / right-sided endocarditis (R-IE) (excluding left-sided endocarditis) in the mITT population. Responder (clinical outcome of improvement or response) was defined as survival with improvement or resolution of attributable signs and symptoms, and without new signs or symptoms, new foci of infection, change in antibiotics due to non-response, complications of S. aureus, or further surgery or medical intervention to treat S. aureus.

Outcome measures

Outcome measures
Measure	CF-301 n=47 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=39 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Clinical Responders at Day 14 in Patients With cBSI/R-IE	36 Participants	22 Participants

POST_HOC outcome

Timeframe: From study drug dosing to hospital discharge (in patients discharged alive) through Day 180

Population: Microbiological Intent-to-Treat (mITT) population

Length of hospital stay in patients enrolled in the United States in the MRSA Subgroup in the mITT population

Outcome measures

Outcome measures
Measure	CF-301 n=25 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=13 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Health Resource Utilization: Length of Hospital Stay	6 days Interval 2.0 to 69.0	10 days Interval 5.0 to 51.0

POST_HOC outcome

Timeframe: Day 30

Population: Microbiological Intent-to-Treat (mITT) population

30-day all-cause mortality in the MRSA subgroup in the mITT

Outcome measures

Outcome measures
Measure	CF-301 n=27 Participants Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=16 Participants Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
All-cause Mortality at Day 30 in MRSA Subgroup	1 Participants	4 Participants

Adverse Events

CF-301

Serious events: 45 serious events

Other events: 62 other events

Deaths: 17 deaths

Placebo

Serious events: 28 serious events

Other events: 39 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

ContraFect

Phone: 914-207-2300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After multi-center publication has been published by sponsor, or if it hasn't been published in 24 months following completion of Clinical Study Report, PI may publish results independently. PI must allow sponsor at least 90 days to review submission, to request deletion of sponsor confidential information (not study results) and in that initial 90 day period, allow delay of up to 60 additional days to allow sponsor to protect its rights to any confidential information.
Publication restrictions are in place

Restriction type: OTHER

Measure	CF-301 n=72 participants at risk Patients received a single IV infusion of CF-301 in addition to standard of care (SOC) antibacterial therapy selected by the investigator.	Placebo n=47 participants at risk Patients received a single IV infusion of placebo in addition to standard of care (SOC) antibacterial therapy selected by the investigator.
Blood and lymphatic system disorders Anemia	6.9% 5/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	8.5% 4/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Gastrointestinal disorders Abdominal pain	0.00% 0/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	8.5% 4/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Gastrointestinal disorders Constipation	12.5% 9/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	10.6% 5/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Gastrointestinal disorders Diarrhea	9.7% 7/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Gastrointestinal disorders Nausea	8.3% 6/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
General disorders Edema peripheral	8.3% 6/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	8.5% 4/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
General disorders Pyrexia	5.6% 4/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Investigations Cardiac murmur	8.3% 6/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	2.1% 1/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Metabolism and nutrition disorders Hypoglycemia	2.8% 2/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Metabolism and nutrition disorders Hypokalemia	6.9% 5/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Musculoskeletal and connective tissue disorders Back pain	2.8% 2/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Nervous system disorders Headache	9.7% 7/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	8.5% 4/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Psychiatric disorders Anxiety	0.00% 0/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Psychiatric disorders Insomnia	5.6% 4/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	2.1% 1/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.9% 5/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Skin and subcutaneous tissue disorders Decubitus ulcer	2.8% 2/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Vascular disorders Hypotension	1.4% 1/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Infections and infestations Urinary tract infection	11.1% 8/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	12.8% 6/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Ear and labyrinth disorders Eye disorders	6.9% 5/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	0.00% 0/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Investigations Blood alkaline phosphatase increased	2.8% 2/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.
Metabolism and nutrition disorders Decreased appetite	1.4% 1/72 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.	6.4% 3/47 • All AEs and SAEs were collected during the core study, from the time of consent through Test of Cure (TOC) between 56-70 days. After completion of the core study, all SAEs were collected during the long-term follow-up through Day 180. All-cause mortality is reported in the intent-to-treat (ITT) population. Serious adverse events and other (not including serious) adverse events are reported in the Safety population.