Trial Outcomes & Findings for Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial (NCT NCT04839354)

Results Overview

The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

271 participants

Primary outcome timeframe

From study drug delivery to last IV opioid treatment (up to 1,724.1 hours)

Results posted on

2025-07-30

Participant Flow

Participants were recruited from ten children's hospitals in the United States. Participant enrollment began June 21, 2021 and all follow-up assessments were completed by July 11, 2024.

Participant milestones

Participant milestones
Measure	L-Arginine Hydrochloride Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Overall Study STARTED	129	142
Overall Study COMPLETED	129	142
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sickle Cell Disease Treatment With Arginine Therapy (STArT) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).	Total n=271 Participants Total of all reporting groups
Age, Continuous	14.8 years n=5 Participants	15.2 years n=7 Participants	15.1 years n=5 Participants
Age, Customized Under 12 years old	36 Participants n=5 Participants	42 Participants n=7 Participants	78 Participants n=5 Participants
Age, Customized 12 to 21 years old	93 Participants n=5 Participants	100 Participants n=7 Participants	193 Participants n=5 Participants
Sex: Female, Male Female	70 Participants n=5 Participants	62 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	80 Participants n=7 Participants	139 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	115 Participants n=5 Participants	135 Participants n=7 Participants	250 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	115 Participants n=5 Participants	134 Participants n=7 Participants	249 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	129 participants n=5 Participants	142 participants n=7 Participants	271 participants n=5 Participants

PRIMARY outcome

Timeframe: From study drug delivery to last IV opioid treatment (up to 1,724.1 hours)

The time-to-crisis resolution is defined as the time in hours from the date and time of the first study drug delivery to time of the last dose of parenteral opioid delivery.

Outcome measures

Outcome measures
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Time-to-crisis Resolution	81.5 hours Standard Deviation 79.6	88.6 hours Standard Deviation 152.2

SECONDARY outcome

Timeframe: From the time of IV placement throughout opioid treatment (up to 1,724.1 hours)

Total parenteral opioid use is assessed as morphine equivalents in milligrams per kilogram (mg/kg).

Outcome measures

Outcome measures
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Total Parenteral Opioid Use	2.6 milligrams per kilogram (mg/kg) Standard Deviation 4.5	1.9 milligrams per kilogram (mg/kg) Standard Deviation 2.8

SECONDARY outcome

Timeframe: Time of presentation and on the day of discharge (up to 554.8 days)

Pain is assessed using a scale from 0 to 10, where 10 is the highest pain level. Daily highest and lowest pain scores are recorded. The change in score is calculated by subtracting the score at discharge from the score at the time of presentation.

Outcome measures

Outcome measures
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Change in Pain Score	3.5 score on a scale Standard Deviation 3.3	3.7 score on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: Within 12 hours of study drug delivery, and on the day of discharge (up to 554.8 days)

The PROMIS Pain Interference instrument is an 8-item, self-administered survey that assesses the interference of pain on daily activities. Participants are asked to respond to questions regarding the extent of their pain. Responses range from 1 to 5, where 1 represents "not at all" and 5 represents "very much". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of pain interference compared to the reference population, while scores higher than 50 indicate greater pain interference compared to the reference population. The change in score is calculated by subtracting the score at the time of discharge from the score from within 12 hours of study drug delivery. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery.

Outcome measures

Outcome measures
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Change in Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Score	3.5 score on a scale Standard Deviation 3.3	3.7 score on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: Within 12 hours of study drug delivery, and on the day of discharge (up to 554.8 days)

The PROMIS Pain Behavior instrument is an 8-item, self-administered survey that assesses external manifestations of pain. Participants are asked to respond to questions regarding the extent of their pain. Responses range from 1 to 5, where 1 represents "never" and 5 represents "always". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of pain behavior compared to the reference population, while scores higher than 50 indicate greater pain behavior compared to the reference population. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery.

Outcome measures

Outcome measures
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Change in PROMIS Pain Behavior Score	0.8 score on a scale Standard Deviation 6.8	1.0 score on a scale Standard Deviation 7.1

SECONDARY outcome

Timeframe: Within 12 hours of study drug delivery and on the day of discharge (up to 554.8 days)

The PROMIS Fatigue instrument is an 8-item, self-administered survey that assesses fatigue level within the past seven days. Participants are asked to respond to questions regarding fatigue frequency. Responses range from 1 to 5, where 1 represents "never" and five represents "always". Total raw scores are converted to T-scores. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Scores below 50 indicate a lower amount of fatigue compared to the reference population, while scores higher than 50 indicate greater fatigue compared to the reference population. The change in score is calculated by subtracting the score at discharge from the score within 12 hours of study drug delivery.

Outcome measures

Outcome measures
Measure	L-Arginine Hydrochloride n=129 Participants Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 Participants Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
Change in PROMIS Fatigue Score	-0.4 score on a scale Standard Deviation 8.1	0.1 score on a scale Standard Deviation 9.1

Adverse Events

L-Arginine Hydrochloride

Serious events: 22 serious events

Other events: 81 other events

Deaths: 0 deaths

Placebo

Serious events: 25 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	L-Arginine Hydrochloride n=129 participants at risk Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 participants at risk Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
General disorders Abdomial pain	7.8% 10/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	3.5% 5/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Respiratory, thoracic and mediastinal disorders Acute chest syndrome	7.0% 9/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	7.0% 10/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Decreased appetite	7.8% 10/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	3.5% 5/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Blood and lymphatic system disorders Decreased haemoglobin	9.3% 12/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	3.5% 5/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Headache	11.6% 15/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	9.9% 14/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Blood and lymphatic system disorders Hypoxemia	5.4% 7/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	7.7% 11/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Nausea	17.8% 23/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	16.2% 23/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Pyrexia	14.0% 18/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	12.7% 18/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Gastrointestinal disorders Vomiting	7.8% 10/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	9.9% 14/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Blood and lymphatic system disorders Transfusion	7.8% 10/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	6.3% 9/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).

Additional Information

Claudia Morris, MD

Emory University

Phone: 404-785-7141

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	L-Arginine Hydrochloride n=129 participants at risk Participants receiving L-arginine hydrochloride in parenteral form. Participants receive up to 21 doses, with participants who are discharged early receiving fewer doses. A one-time L-arginine hydrochloride loading dose of 200 mg/kg is administered intravenously (IV) followed by a standard dose of 100 mg/kg given by IV three times per day (TID).	Placebo n=142 participants at risk Participants receiving normal saline as a placebo for L-arginine hydrochloride for up to 21 doses, with participants who are discharged early receiving fewer doses. A placebo of normal saline is administered by IV with a loading dose of 2ml/kg followed by 1ml/kg given by IV three times per day (TID).
General disorders Pain	4.7% 6/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	6.3% 9/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Sickle cell anaemia with crisis	7.8% 10/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	5.6% 8/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Blood and lymphatic system disorders Acidosis	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Respiratory, thoracic and mediastinal disorders Acute chest syndrome	1.6% 2/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	2.8% 4/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.70% 1/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Asthenia	0.00% 0/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.70% 1/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Drug dependence	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Gastrointestinal disorders Gastroenteritis	0.00% 0/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.70% 1/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Hallucination	0.00% 0/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.70% 1/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Intensive care	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Psychiatric disorders Intentional overdose	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Musculoskeletal and connective tissue disorders Limb discomfort	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
General disorders Pyrexia	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.78% 1/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.00% 0/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/129 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).	0.70% 1/142 • Information on adverse events was collected beginning at the time of randomization through Day 9 or hospital discharge or emergency department discharge (whichever comes first, up to 9 days). Emergency department revisits and hospital admissions were tracked through 28 days following hospital or emergency discharge and entered as adverse events or serious adverse events (up to 583 days).