Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Danirixin Co-administered With Oseltamivir in the Treatment of Adults Hospitalized With Influenza (NCT NCT02927431)

Last Updated: 2020-11-30

Results Overview

The clinical response was defined as Hospital discharge due to clinical improvement OR normalization of temperature; and oxygen saturation; and respiratory status/heart rate/systolic blood pressure (normalization of 2 out of these 3 parameters). The clinical response based on vital signs/ventilation status required 24-hour confirmation. Considering 2-hour assessment window, the response confirmation period was 22 hours. Kaplan Meier estimates for the median of TTCR was provided. One participant had vital sign resolution at Baseline and was counted as having a clinical response but was not included in the Kaplan Meier Estimates. Influenza Positive Population (IPP) Population comprised of all participants in the Intent to Treat Exposed (ITT-E) Population with influenza infection (positive influenza Polymerase Chain Reaction \[PCR\] or culture at any time point) confirmed by central lab testing. Only those participants with data available at the indicated time point were analyzed.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Up to 45 Days

Results posted on

2020-11-30

Participant Flow

This was a randomized study to evaluate the efficacy and safety of Danirixin (DNX) co-administered with a standard-of-care antiviral (oseltamivir \[OSV\]), in the treatment of adults hospitalized with influenza. The study enrolled participants in 7 centers across 3 countries (Romania,Sweden and United States) and was terminated due to poor enrollment

A total of 14 participants were screened for the study, of which 4 participants were screening failures. 10 participants received study treatment.

Participant milestones

Participant milestones
Measure	Placebo + OSV Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 milligram (mg) twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Overall Study STARTED	2	4	4
Overall Study COMPLETED	2	4	3
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + OSV Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 milligram (mg) twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Danirixin Co-administered With Oseltamivir in the Treatment of Adults Hospitalized With Influenza

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	Total n=10 Participants Total of all reporting groups
Age, Continuous	61.0 Years STANDARD_DEVIATION 24.04 • n=5 Participants	66.0 Years STANDARD_DEVIATION 8.76 • n=7 Participants	63.0 Years STANDARD_DEVIATION 24.90 • n=5 Participants	63.8 Years STANDARD_DEVIATION 17.34 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Race/ Ethnicity · African American/African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race/ Ethnicity · Asian-Central/South Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race/ Ethnicity · White-White/Caucasian/European Heritage	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 45 Days

Population: IPP Population

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=3 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Time to Clinical Response (TTCR)	1.33 Days Interval 0.71 to 1.95	4.53 Days Interval 2.95 to 5.71	4.76 Days Interval 3.66 to 5.08

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population

Time to Respiratory Response was defined as meeting at least one of the following criteria, and maintained for 24 hours: return to pre-morbid oxygen requirement (participants with chronic oxygen use or ventilator support), or return to no requirement of supplemental oxygen, or respiratory rate \<=24 per minute (without supplemental oxygen). Kaplan Meier estimates for the median of TTRR for each treatment group was provided. NA indicates data is not available. Due to limited data, no TTRR estimate could be calculated for any of the treatment groups.

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Time to Respiratory Response (TTRR)	NA Days Interval 1.95 to Data could not be calculated due to insufficient number of participants with events.	NA Days Interval 1.07 to Data could not be calculated due to insufficient number of participants with events.	NA Days Interval 3.04 to Data could not be calculated due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Time from first dose of treatment to time to afebrile status (\<=36.6 degree celsius-axilla/temporal or \<=37.2 degree celsius- oral, or \<=37.7 degree celsius-rectal/core, tympanic) was to be evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Time from first dose of treatment to time of improved oxygen saturation was to be calculated. A participant with a history of chronic hypoxia (without supplemental oxygen) satisfied normalization criteria for oxygen saturation if the value (without supplemental oxygen) is \<=2 percent from participant's historical oxygen saturation Baseline as recorded within 12 months prior to enrollment as documented in the participant's medical records. This requirement was to be waived for participants with a history of chronic supplemental oxygen requirement who had a Baseline oxygen saturation \<95 percent with supplemental oxygen, within 12 months prior to enrollment as documented in the participant's medical records.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Time from first dose of treatment to time of heart rate \<=100 beats per minute was to be evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Time from first dose of treatment to time of SBP at \>=90 millimeters of mercury (mmHg) was to be evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Percentage of Participants With Clinical Response Over Time	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population

The Respiratory Response was defined as meeting at least one of the following criteria, and maintained for 24 hours: return to pre-morbid oxygen requirement (participants with chronic oxygen use or ventilator support), or return to no requirement of supplemental oxygen, or respiratory rate \<=24 per minute (without supplemental oxygen). Percentage of participants with improved respiratory status has been presented.

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Percentage of Participants With Improved Respiratory Status Over Time	50 Percentage of Participants	50 Percentage of Participants	50 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Time to improvement of ventilation status was assessed by modality, frequencies and durations of invasive and non-invasive ventilator support, duration of oxygen supplementation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Number of days of stay in the ICU over the treatment period and post treatment period was to be recorded.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Number of participants requiring ICU admission during treatment period and after post treatment was to be recorded.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Number of days of stay in the hospital over treatment period and post treatment period was to be recorded.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Development of septic shock was to be assessed by occurrence of hypotension requiring vasopressive therapy and serum lactate level \>2 millimeter (mm) after adequate fluid resuscitation. Number of participants with development of septic shock were planned to be presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population

Complications of influenza such as bacterial pneumonia, pneumothorax, pleural effusion, acute respiratory distress syndrome (ARDS), myositis, encephalitis, myocarditis, and associated antibiotic use was recorded. Number of participants who reqruied use of associated antibiotics for complications of influenza is presented.

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Number of Participants Used Antibiotics for Complications of Influenza	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 45 Days

Population: IPP Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed.

Number of participants with improvement in ordinal scale of clinical efficacy over time was to be assessed by: death, mechanical vent, in the ICU, non-ICU hospitalization, and hospital discharge.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 45 Days

Population: Safety Population

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. Participants who received any of the study treatment and had any AE or SAE or AESI were considered for analysis. Safety Population comprised of all participants who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs of Special Interest (AESIs) Any non-SAE	0 Participants	4 Participants	4 Participants
Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs of Special Interest (AESIs) Any SAE	0 Participants	0 Participants	2 Participants
Number of Participants With Any Non-serious Adverse Event (AE); Any Serious AE (SAE); Any AEs of Special Interest (AESIs) Any AESI	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and up to 45 days

Population: Safety Population

Blood samples were collected to evaluate albumin and total protein at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data is not available.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to 45 days

Population: Safety Population

Blood samples were collected to evaluate WBC and ANC at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data is not available.

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 4, n=0,2,1	—	1.15 Giga cells per Liter (GI/L) Standard Deviation 3.889	-7.10 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 4, n=0,2,1	—	1.410 Giga cells per Liter (GI/L) Standard Deviation 3.2810	-7.420 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Discharge/Day 45, n=2,3,1	-4.650 Giga cells per Liter (GI/L) Standard Deviation 1.9092	3.050 Giga cells per Liter (GI/L) Standard Deviation 2.9511	-9.720 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 3 post last dose, n=1,4,1	-4.60 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	1.95 Giga cells per Liter (GI/L) Standard Deviation 2.594	-8.00 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 2, n=1,0,0	-2.70 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 3, n=1,1,0	-5.10 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.00 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 5, n=1,1,1	-2.90 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.70 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.30 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 6, n=1,0,0	-2.40 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 7, n=1,0,0	-2.90 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Day 8, n=1,0,0	-3.10 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) WBC, Discharge/Day 45, n=2,3,1	-3.55 Giga cells per Liter (GI/L) Standard Deviation 2.051	3.97 Giga cells per Liter (GI/L) Standard Deviation 2.765	-9.50 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 2, n=1,0,0	-3.880 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 3, n=1,1,0	-5.640 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.070 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 5, n=1,1,1	-4.250 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.250 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-6.260 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 6, n=1,0,0	-3.540 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 7, n=1,0,0	-4.180 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 8, n=1,0,0	-4.580 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in White Blood Cell Count (WBC) and Absolute Neutrophil Count (ANC) ANC, Day 3 post last dose, n=1,4,1	-5.680 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	1.033 Giga cells per Liter (GI/L) Standard Deviation 2.9818	-9.060 Giga cells per Liter (GI/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.

SECONDARY outcome

Timeframe: Baseline and up to 45 days

Population: Safety Population

Blood samples were collected to evaluate T. Bilirubin, creatinine and D. Bilirubin at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data is not available.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to 45 days

Population: Safety Population

Blood samples were collected to evaluate ALT, AST and ALP at indicated time points. Values at Day 1 were considered as Baseline values. Change from Baseline at each visit was calculated by subtracting Baseline value from post-dose visit value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data is not available.

Outcome measures

SECONDARY outcome

Timeframe: Up to 6 days

Population: Safety Population

Single 12-lead ECGs were obtained at Baseline and on the day of last dose during the study using an ECG machine that automatically calculates the heart rate (HR) and measures PR, QRS, QT, and QT duration corrected for heart rate (QTc). Number of participants with clinically significant abnormality in ECG are presented.

Outcome measures

Outcome measures
Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose

Population: PK Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited sample size.

Cmax of IV DNX was to be derived from the Pharmacokinetics (PK) samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose. PK Population comprised of all participants who underwent blood PK sampling during the study and from whom one or more blood concentration was determined.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose

Population: PK Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited sample size.

AUC (0-t) of IV DNX was to be derived from the PK samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose

Population: PK Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited PK parameters available.

Tmax of IV DNX was to be derived from the PK samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose

Population: PK Population. As the study was terminated, only a selected set of originally planned analysis were performed and hence this endpoint was not analyzed due to limited sample size.

Cavg of IV DNX was to be derived from the PK samples collected at Day 1 pre-dose, Day 3 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose and Day 5 pre-dose.

Outcome measures

Outcome data not reported

Adverse Events

Placebo + OSV

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

DNX 15 mg + OSV

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

DNX 50 mg + OSV

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo + OSV n=2 participants at risk Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 participants at risk Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 participants at risk Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Cardiac disorders Cardiac failure	0.00% 0/2 • On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45. On treatment SAEs and non-serious AEs were reported for the Safety Population.	0.00% 0/4 • On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45. On treatment SAEs and non-serious AEs were reported for the Safety Population.	25.0% 1/4 • On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45. On treatment SAEs and non-serious AEs were reported for the Safety Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/2 • On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45. On treatment SAEs and non-serious AEs were reported for the Safety Population.	0.00% 0/4 • On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45. On treatment SAEs and non-serious AEs were reported for the Safety Population.	25.0% 1/4 • On-treatment SAEs and non-serious AEs were collected from the start of the study treatment up to Day 45. On treatment SAEs and non-serious AEs were reported for the Safety Population.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Change From Baseline in Albumin and Total Protein Albumin, Day 3, n=1,2,2	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.0 Gram per Liter (G/L) Standard Deviation 1.41	-2.0 Gram per Liter (G/L) Standard Deviation 2.83
Change From Baseline in Albumin and Total Protein Albumin, Day 2, n=1,0,0	2.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Albumin and Total Protein Albumin, Day 2, sample 2, n=0,0,1	—	—	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Albumin and Total Protein Albumin, Day 3, sample 2, n=0,1,2	—	-9.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.5 Gram per Liter (G/L) Standard Deviation 4.95
Change From Baseline in Albumin and Total Protein Albumin, Day 4, n=0,1,2	—	-1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.0 Gram per Liter (G/L) Standard Deviation 4.24
Change From Baseline in Albumin and Total Protein Albumin, Day 4, sample 2, n=0,1,1	—	-8.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Albumin and Total Protein Albumin, Day 5, n=1,1,3	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.7 Gram per Liter (G/L) Standard Deviation 6.03
Change From Baseline in Albumin and Total Protein Albumin, Day 6, n=1,1,4	1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-6.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.8 Gram per Liter (G/L) Standard Deviation 4.99
Change From Baseline in Albumin and Total Protein Albumin, Day 7, n=1,1,1	-2.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Albumin and Total Protein Albumin, Day 8, n=1,0,0	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Albumin and Total Protein Albumin, Discharge/Day 45, n=2,2,3	2.5 Gram per Liter (G/L) Standard Deviation 2.12	-0.5 Gram per Liter (G/L) Standard Deviation 0.71	5.7 Gram per Liter (G/L) Standard Deviation 6.81
Change From Baseline in Albumin and Total Protein Albumin, Day 3 post last dose, n=1,3,3	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-1.3 Gram per Liter (G/L) Standard Deviation 1.15	-2.3 Gram per Liter (G/L) Standard Deviation 1.15
Change From Baseline in Albumin and Total Protein Total Protein, Day 2, n=1,0,1	1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	-1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Albumin and Total Protein Total Protein, Day 3, n=1,2,2	1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.5 Gram per Liter (G/L) Standard Deviation 4.95	-3.0 Gram per Liter (G/L) Standard Deviation 4.24
Change From Baseline in Albumin and Total Protein Total Protein, Day 3, sample 2, n=0,1,2	—	-13.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.0 Gram per Liter (G/L) Standard Deviation 4.24
Change From Baseline in Albumin and Total Protein Total Protein, Day 4, n=0,1,2	—	-1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.0 Gram per Liter (G/L) Standard Deviation 5.66
Change From Baseline in Albumin and Total Protein Total Protein, Day 4, sample 2, n=0,1,1	—	-10.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-7.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Albumin and Total Protein Total Protein, Day 5, n=1,1,3	-1.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-7.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.7 Gram per Liter (G/L) Standard Deviation 10.97
Change From Baseline in Albumin and Total Protein Total Protein, Day 6, n=1,1,4	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-7.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.0 Gram per Liter (G/L) Standard Deviation 6.98
Change From Baseline in Albumin and Total Protein Total Protein, Day 7, n=1,1,1	-3.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Albumin and Total Protein Total Protein, Day 8, n=1,0,0	0.0 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Albumin and Total Protein Total Protein, Discharge/Day 45, n=2,2,3	0.0 Gram per Liter (G/L) Standard Deviation 2.83	-1.5 Gram per Liter (G/L) Standard Deviation 2.12	6.7 Gram per Liter (G/L) Standard Deviation 11.02
Change From Baseline in Albumin and Total Protein Total Protein, Day 3 post last dose, n=1,3,3	-0.3 Gram per Liter (G/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.0 Gram per Liter (G/L) Standard Deviation 2.00	-3.3 Gram per Liter (G/L) Standard Deviation 3.51

Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 3 post last dose, n=1,3,3	-23.00 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.47 Micromole per Liter (µmol/L) Standard Deviation 9.750	2.93 Micromole per Liter (µmol/L) Standard Deviation 9.304
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 3, n=1,2,2	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.0 Micromole per Liter (µmol/L) Standard Deviation 0.00	0.0 Micromole per Liter (µmol/L) Standard Deviation 2.83
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 3, sample 2, n=0,2,4	—	-9.30 Micromole per Liter (µmol/L) Standard Deviation 6.930	1.32 Micromole per Liter (µmol/L) Standard Deviation 8.397
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 4, n=1,3,4	-39.80 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.90 Micromole per Liter (µmol/L) Standard Deviation 6.222	-4.20 Micromole per Liter (µmol/L) Standard Deviation 6.975
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 4, sample 2, n=0,2,3	—	0.45 Micromole per Liter (µmol/L) Standard Deviation 15.627	-2.40 Micromole per Liter (µmol/L) Standard Deviation 7.375
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 5, n=1,2,3	-40.60 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-1.35 Micromole per Liter (µmol/L) Standard Deviation 9.405	-2.67 Micromole per Liter (µmol/L) Standard Deviation 4.070
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 5, sample 2, n=0,1,0	—	-15.90 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 6, n=1,1,4	-44.20 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-10.60 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	3.52 Micromole per Liter (µmol/L) Standard Deviation 4.396
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 7, n=1,1,1	-38.00 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-10.60 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-1.80 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 8, n=1,0,0	-26.50 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Discharge/Day 45, n=2,2,3	-16.80 Micromole per Liter (µmol/L) Standard Deviation 22.486	-3.55 Micromole per Liter (µmol/L) Standard Deviation 8.697	6.50 Micromole per Liter (µmol/L) Standard Deviation 4.521
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 2, n=1,0,0	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 2, sample 2, n=0,0,1	—	—	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 3, sample 2, n=0,1,2	—	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation 2.83
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 4, n=0,1,2	—	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation 0.00
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 4, sample 2, n=0,1,1	—	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 5, n=1,1,3	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation 2.00
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 6, n=1,1,4	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-0.5 Micromole per Liter (µmol/L) Standard Deviation 1.91
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 7, n=1,1,1	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 8, n=1,0,0	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Discharge/Day 45, n=2,2,3	-3.0 Micromole per Liter (µmol/L) Standard Deviation 4.24	-1.0 Micromole per Liter (µmol/L) Standard Deviation 1.41	-0.7 Micromole per Liter (µmol/L) Standard Deviation 1.15
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) D. Bilirubin, Day 3 post last dose, n=1,3,3	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation 0.00	0.7 Micromole per Liter (µmol/L) Standard Deviation 2.31
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 2, n=1,0,0	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 2, sample 2, n=0,0,1	—	—	-4.00 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 3, n=1,2,2	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.0 Micromole per Liter (µmol/L) Standard Deviation 2.828	-1.00 Micromole per Liter (µmol/L) Standard Deviation 1.414
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 3, sample 2, n=0,1,2	—	-6.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.00 Micromole per Liter (µmol/L) Standard Deviation 0.000
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 4, n=0,1,2	—	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.00 Micromole per Liter (µmol/L) Standard Deviation 2.828
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 4, sample 2, n=0,1,1	—	-6.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.00 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 5, n=1,1,3	0.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.67 Micromole per Liter (µmol/L) Standard Deviation 1.155
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 6, n=1,1,4	-2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-0.50 Micromole per Liter (µmol/L) Standard Deviation 1.000
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 7, n=1,1,1	-6.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	2.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.00 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 8, n=1,0,0	-6.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Discharge/Day 45, n=2,2,3	-1.0 Micromole per Liter (µmol/L) Standard Deviation 1.414	0.0 Micromole per Liter (µmol/L) Standard Deviation 2.828	-0.67 Micromole per Liter (µmol/L) Standard Deviation 1.155
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) T. Bilirubin, Day 3 post last dose, n=1,3,3	-4.0 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 Micromole per Liter (µmol/L) Standard Deviation 2.000	-4.60 Micromole per Liter (µmol/L) Standard Deviation 4.503
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 2, n=2,2,4	-7.95 Micromole per Liter (µmol/L) Standard Deviation 18.738	-0.50 Micromole per Liter (µmol/L) Standard Deviation 5.657	-3.35 Micromole per Liter (µmol/L) Standard Deviation 1.323
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 2, sample 2, n=1,1,2	3.50 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	7.90 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-8.40 Micromole per Liter (µmol/L) Standard Deviation 0.566
Change From Baseline in Total Bilirubin (T. Bilirubin), Creatinine and Direct Bilirubin (D. Bilirubin) Creatinine, Day 3, n=1,2,3	-33.60 Micromole per Liter (µmol/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.60 Micromole per Liter (µmol/L) Standard Deviation 1.273	-4.77 Micromole per Liter (µmol/L) Standard Deviation 1.012

Measure	Placebo + OSV n=2 Participants Participants received matching placebo given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 15 mg + OSV n=4 Participants Participants received DNX 15 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.	DNX 50 mg + OSV n=4 Participants Participants received DNX 50 mg given as a 1 hour infusion twice daily for up to 5 days. Infusion was administered at a constant rate over approximately 1 hour +- 10 minutes and approximately 12 hours apart +- 1 hour. All participants also received open-label oral OSV 75 mg twice daily given as standard of care. The investigator could elect to continue treatment with OSV after 5 days of study treatment.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 2, n=1,0,0	10.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 2, sample 2, n=0,0,1	—	—	-1.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 3, n=1,2,2	4.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	3.0 International unit per Liter (IU/L) Standard Deviation 1.41	2.0 International unit per Liter (IU/L) Standard Deviation 5.66
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 3, sample 2, n=0,1,2	—	-1.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-1.0 International unit per Liter (IU/L) Standard Deviation 5.66
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 4, n=0,1,2	—	-18.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-3.5 International unit per Liter (IU/L) Standard Deviation 2.12
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 5, n=1,1,3	-10.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-9.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-7.3 International unit per Liter (IU/L) Standard Deviation 2.08
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 4, sample 2, n=0,1,1	—	1.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	10.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 5, n=1,1,3	0.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-0.3 International unit per Liter (IU/L) Standard Deviation 3.79
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 6, n=1,1,4	-1.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-37.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-2.3 International unit per Liter (IU/L) Standard Deviation 3.86
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 7, n=1,1,1	-2.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-42.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-6.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 8, n=1,0,0	-1.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Discharge/Day 45, n=2,2,3	-6.0 International unit per Liter (IU/L) Standard Deviation 4.24	-30.0 International unit per Liter (IU/L) Standard Deviation 35.36	0.7 International unit per Liter (IU/L) Standard Deviation 2.08
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALT, Day 3 post last dose, n=1,3,3	2.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-17.0 International unit per Liter (IU/L) Standard Deviation 19.08	-4.0 International unit per Liter (IU/L) Standard Deviation 3.61
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 2, n=1,0,0	14.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 2, sample 2, n=0,0,1	—	—	-4.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 3, n=1,2,2	11.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	6.0 International unit per Liter (IU/L) Standard Deviation 8.49	-2.0 International unit per Liter (IU/L) Standard Deviation 2.83
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 3, sample 2, n=0,1,2	—	8.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-1.5 International unit per Liter (IU/L) Standard Deviation 4.95
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 4, n=0,1,2	—	-29.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-8.0 International unit per Liter (IU/L) Standard Deviation 2.83
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 4, sample 2, n=0,1,1	—	16.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	0.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 6, n=1,1,4	-12.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-46.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.8 International unit per Liter (IU/L) Standard Deviation 7.32
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 7, n=1,1,1	-11.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-51.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-11.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 8, n=1,0,0	-12.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Discharge/Day 45, n=2,2,3	-12.0 International unit per Liter (IU/L) Standard Deviation 11.31	-27.5 International unit per Liter (IU/L) Standard Deviation 30.41	-3.0 International unit per Liter (IU/L) Standard Deviation 5.57
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) AST, Day 3 post last dose, n=1,3,3	-10.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-21.7 International unit per Liter (IU/L) Standard Deviation 23.76	-10.7 International unit per Liter (IU/L) Standard Deviation 5.86
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 2, n=1,0,0	8.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 2,sample 2, n=0,0,1	—	—	-3.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 3, n=1,2,2	2.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-6.0 International unit per Liter (IU/L) Standard Deviation 8.49	-8.0 International unit per Liter (IU/L) Standard Deviation 2.83
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 3, sample 2, n=0,1,2	—	-23.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-14.0 International unit per Liter (IU/L) Standard Deviation 7.07
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 4, n=0,1,2	—	-25.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-5.5 International unit per Liter (IU/L) Standard Deviation 0.71
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 4, sample 2, n=0,1,1	—	-22.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-4.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 5, n=1,1,3	6.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-8.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-11.0 International unit per Liter (IU/L) Standard Deviation 7.81
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 6, n=1,1,4	5.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-51.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-9.5 International unit per Liter (IU/L) Standard Deviation 8.19
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 7, n=1,1,1	2.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-50.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	17.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Discharge/Day 45, n=2,2,3	10.0 International unit per Liter (IU/L) Standard Deviation 0.00	-25.5 International unit per Liter (IU/L) Standard Deviation 30.41	2.0 International unit per Liter (IU/L) Standard Deviation 9.64
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 3 post last dose, n=1,3,3	1.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	-19.7 International unit per Liter (IU/L) Standard Deviation 22.03	-9.3 International unit per Liter (IU/L) Standard Deviation 7.51
Change From Baseline in Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST) and Alkaline Phosphatase (ALP) ALP, Day 8, n=1,0,0	3.0 International unit per Liter (IU/L) Standard Deviation NA NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.	—	—