Trial Outcomes & Findings for Study to Determine Safety and Dosage of OPTISON in Pediatric Participants (NCT NCT03740997)

Last Updated: 2024-05-17

Results Overview

Visualization of each of the 12 segments of the LV wall in standard A4C and A2C views were measured by the qualitative EBD visualization scale: score 0 =no visualization of the LV endocardial border; 1 =poor visualization; 2 =fair visualization; 3 =good/optimal visualization. The total LV EBD score was calculated as the sum of the individual scores assigned to each of the 12 LV wall segment and the total score ranged from 0 (no visualization of the LV endocardial border) to 36 (good/optimal visualization). A higher score indicated better visualization. The total score of qualitative EBD visualization scale were reported by reader (independent blinded), non-contrast and dose levels.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

39 participants

Primary outcome timeframe

Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Results posted on

2024-05-17

Participant Flow

This study was conducted between 01 December 2020 to 30 March 2023 at 8 centers in the United States.

A total 39 participants were enrolled into the study, of which 37 received OPTISON injections according to body weight (less than or equal to \[\<=40\] kilograms \[kg\] \[included participants with body weight more than or equal to \[\>=\] 20 to \<=28 kg and greater than \[\>\] 28 to \<=40 kg\] and \>40 kg). As pre planned in Statistical Analysis Plan, data were collected, analyzed and presented for two body weight categories (\<= 40 kg and \>40 kg) only in all sections of the result.

Participant milestones

Participant milestones
Measure	Body Weight Group >40 kg: OPTISON Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level. The 37 treated subjects received both dose levels. Per protocol, up to 3 injections per dose level were allowed for acquiring different imaging views. A maximum of 2 injections was recorded in the treated population.	Body Weight Group <=40 kg: OPTISON Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 milliliter (mL; dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) intravenous (IV) injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively. The 37 treated subjects received both dose levels. Per protocol, up to 3 injections per dose level were allowed for acquiring different imaging views. A maximum of 2 injections was recorded in the treated population.
Overall Study STARTED	31	8
Overall Study Safety Population (Treated)	29	8
Overall Study Per-protocol (PP) Population	23	7
Overall Study COMPLETED	29	8
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Body Weight Group >40 kg: OPTISON Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level. The 37 treated subjects received both dose levels. Per protocol, up to 3 injections per dose level were allowed for acquiring different imaging views. A maximum of 2 injections was recorded in the treated population.	Body Weight Group <=40 kg: OPTISON Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 milliliter (mL; dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) intravenous (IV) injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively. The 37 treated subjects received both dose levels. Per protocol, up to 3 injections per dose level were allowed for acquiring different imaging views. A maximum of 2 injections was recorded in the treated population.
Overall Study Withdrawal by Subject	1	0
Overall Study Participant was unable to complete study procedures	1	0

Baseline Characteristics

Study to Determine Safety and Dosage of OPTISON in Pediatric Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Total n=37 Participants Total of all reporting groups
Age, Continuous	10.4 years STANDARD_DEVIATION 1.60 • n=93 Participants	14.3 years STANDARD_DEVIATION 2.09 • n=4 Participants	13.4 years STANDARD_DEVIATION 2.56 • n=27 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	11 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	18 Participants n=4 Participants	23 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	15 Participants n=4 Participants	18 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=93 Participants	13 Participants n=4 Participants	18 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	20 Participants n=4 Participants	26 Participants n=27 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants

PRIMARY outcome

Timeframe: Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Population: PP population consisted of all participants who had available non-contrast harmonic images and OPTISON-enhanced echocardiographic images, irrespective of the quality of CE-echo and who did not have an important protocol deviation impacting study primary endpoint. Each participant underwent an echocardiographic procedure first without contrast administration, then intravenous bolus injection of OPTISON. Here, "Number Analyzed" signifies participants who were evaluable for specified categories.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=23 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=7 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 1: Non-contrast	10.0 score on a scale Standard Deviation 7.02	15.9 score on a scale Standard Deviation 5.73
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 1: OPTISON Dose Level 1	26.6 score on a scale Standard Deviation 12.50	31.3 score on a scale Standard Deviation 6.53
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 1: OPTISON Dose Level 2	28.6 score on a scale Standard Deviation 10.36	35.1 score on a scale Standard Deviation 2.27
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 2: Non-contrast	8.5 score on a scale Standard Deviation 6.49	13.4 score on a scale Standard Deviation 2.57
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 2: OPTISON Dose Level 1	28.1 score on a scale Standard Deviation 10.34	32.8 score on a scale Standard Deviation 1.47
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 2: OPTISON Dose Level 2	29.7 score on a scale Standard Deviation 10.10	35.4 score on a scale Standard Deviation 0.79
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 3: Non-contrast	12.5 score on a scale Standard Deviation 9.56	21.3 score on a scale Standard Deviation 7.13
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 3: OPTISON Dose Level 1	27.8 score on a scale Standard Deviation 10.40	32.5 score on a scale Standard Deviation 3.73
Mean Total Visualization Score of Qualitative Endocardial Border Delineation (EBD) of the 12 Segments of the Left Ventricle (LV) Wall in Standard Apical 4-chamber (A4C) and Apical 2-chamber (A2C) Reader 3: OPTISON Dose Level 2	28.3 score on a scale Standard Deviation 8.41	33.4 score on a scale Standard Deviation 2.07

SECONDARY outcome

Timeframe: 0- 72 hours

Population: The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.

An Adverse Event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that starts or worsens at or after the time of first dosing of OPTISON.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	9 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1

Population: The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study. Here, "Number Analyzed" signifies participants who were evaluable at specified timepoints.

Systolic and diastolic blood pressure were measured from the arm contra-lateral to the site of OPTISON administration whenever possible and before measurement, participants rested for at least 5 minutes (if possible).

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at 10 Minutes Post Last Dose	-4.6 millimeter of mercury (mmHg) Standard Deviation 10.46	-3.3 millimeter of mercury (mmHg) Standard Deviation 8.21
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at 60 Minutes Post Last Dose	-3.8 millimeter of mercury (mmHg) Standard Deviation 12.01	-4.8 millimeter of mercury (mmHg) Standard Deviation 4.68
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at 10 Minutes Post Last Dose	-2.5 millimeter of mercury (mmHg) Standard Deviation 11.67	-2.8 millimeter of mercury (mmHg) Standard Deviation 5.37
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at 60 Minutes Post Last Dose	-1.1 millimeter of mercury (mmHg) Standard Deviation 9.95	-1.8 millimeter of mercury (mmHg) Standard Deviation 4.65

SECONDARY outcome

Timeframe: Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1

Before heart rate was measured, participants rested for at least 5 minutes (if possible).

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Change From Baseline in Heart Rate Change at 10 Minutes Post Last Dose	-4.9 beats per minute Standard Deviation 9.79	-3.1 beats per minute Standard Deviation 7.90
Change From Baseline in Heart Rate Change at 60 Minutes Post Last Dose	-2.1 beats per minute Standard Deviation 11.31	-3.8 beats per minute Standard Deviation 15.69

SECONDARY outcome

Timeframe: Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1

Before respiratory rate was measured, participants rested for at least 5 minutes (if possible).

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Change From Baseline in Respiratory Rate Change at 10 Minutes Post Last Dose	-0.2 breaths per minute Standard Deviation 3.71	-0.8 breaths per minute Standard Deviation 3.99
Change From Baseline in Respiratory Rate Change at 60 Minutes Post Last Dose	-1.5 breaths per minute Standard Deviation 4.30	-0.8 breaths per minute Standard Deviation 1.49

SECONDARY outcome

Timeframe: Baseline (pre-dose), and at 10 and 60 minutes post last dose on Day 1

Oxygen saturation was measured by pulse oximetry. Before oxygen saturation was measured, participants rested for at least 5 minutes (if possible).

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Change From Baseline in Oxygen Saturation as Measured by Pulse Oximetry Change at 10 Minutes Post Last Dose	0.1 percentage of oxygen saturation Standard Deviation 1.19	0.0 percentage of oxygen saturation Standard Deviation 1.20
Change From Baseline in Oxygen Saturation as Measured by Pulse Oximetry Change at 60 Minutes Post Last Dose	-0.2 percentage of oxygen saturation Standard Deviation 1.32	-0.5 percentage of oxygen saturation Standard Deviation 2.07

SECONDARY outcome

Timeframe: From first dose (Day 1) of study drug to 60 minutes post last dose on Day 1

Population: The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.

Participants underwent assessments including general appearance, respiratory, cardiovascular and neurological (motor function, level of consciousness, sensory function) examination. Any abnormal clinically significant physical examination findings were based on investigator decision.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants With Clinically Significant Abnormality in Physical Examination Findings	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (pre-dose), and at 10 and 30 minutes post last dose on Day 1

Population: The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.

Change from baseline in PR, QRS, QT, Bazett's formula corrected QT (QTcB), Fridericia's formula corrected QT (QTcF) and RR intervals expressed in millisecond (ms) were reported.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=29 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=8 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters PR Interval: Change at 10 Minutes Post Last Dose	-2.0 milliseconds (ms) Standard Deviation 9.47	-2.5 milliseconds (ms) Standard Deviation 4.14
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters PR Interval: Change at 30 Minutes Post Last Dose	-0.1 milliseconds (ms) Standard Deviation 10.26	-3.0 milliseconds (ms) Standard Deviation 6.97
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QRS Duration: Change at 10 Minutes Post Last Dose	-0.2 milliseconds (ms) Standard Deviation 5.35	-0.8 milliseconds (ms) Standard Deviation 5.37
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QRS Duration: Change at 30 Minutes Post Last Dose	-0.4 milliseconds (ms) Standard Deviation 4.05	0.9 milliseconds (ms) Standard Deviation 2.80
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QT Interval: Change at 10 Minutes Post Last Dose	0.0 milliseconds (ms) Standard Deviation 25.83	-6.9 milliseconds (ms) Standard Deviation 26.28
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QT Interval: Change at 30 Minutes Post Last Dose	-1.9 milliseconds (ms) Standard Deviation 23.78	-8.0 milliseconds (ms) Standard Deviation 13.75
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QTcB Interval: Change at 10 Minutes Post Last Dose	-3.8 milliseconds (ms) Standard Deviation 39.57	1.2 milliseconds (ms) Standard Deviation 56.80
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QTcB Interval: Change at 30 Minutes Post Last Dose	-8.6 milliseconds (ms) Standard Deviation 36.21	-9.3 milliseconds (ms) Standard Deviation 30.94
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QTcF Interval: Change at 10 Minutes Post Last Dose	-2.5 milliseconds (ms) Standard Deviation 33.58	-1.9 milliseconds (ms) Standard Deviation 44.56
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters QTcF Interval: Change at 30 Minutes Post Last Dose	-6.2 milliseconds (ms) Standard Deviation 30.48	-8.9 milliseconds (ms) Standard Deviation 24.24
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters RR Interval: Change at 10 Minutes Post Last Dose	15.9 milliseconds (ms) Standard Deviation 60.56	-20.5 milliseconds (ms) Standard Deviation 138.34
Change From Baseline in 12-lead Electrocardiograms (ECGs) Parameters RR Interval: Change at 30 Minutes Post Last Dose	22.8 milliseconds (ms) Standard Deviation 73.59	1.6 milliseconds (ms) Standard Deviation 72.95

SECONDARY outcome

Timeframe: Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Population: PP population consisted of all participants who had available non-contrast harmonic images and OPTISON-enhanced echocardiographic images, irrespective of the quality of CE-echo and who did not have an important protocol deviation impacting study primary endpoint. Here, "Number Analyzed" signifies participants who were evaluable for specified categories.

LVO peak contrast intensity was determined by readers (independent blinded) using a categorical scale as None, Low, Medium, High or Blooming, where, None = Absence of contrast signal; Low = Limited capacity to make a diagnostic assessment; Presence of contrast signal does not improve diagnostic interpretability to a great degree; Medium = Good capacity to make a diagnostic assessment; Contrast signal facilitates diagnostic interpretability to a good degree; High = Optimal capacity to make a diagnostic assessment; Contrast signal facilitates diagnostic interpretability to a high degree; Blooming = Oversaturation of the signal disrupts diagnostic interpretability. Tissue boundaries become challenging to delineate. There may be excessive acoustic shadowing in the far-field of the image. Number of participants by degree of LVO assessed by visual peak contrast intensity was presented by readers and dose levels.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=23 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=7 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 1 · None	2 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 1 · Low	0 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 1 · Medium	8 Participants	2 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 1 · High	12 Participants	4 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 1 · Blooming	0 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 2 · None	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 2 · Low	0 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 2 · Medium	5 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 2 · High	16 Participants	7 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 1: OPTISON Dose Level 2 · Blooming	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 1 · None	2 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 1 · Low	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 1 · Medium	10 Participants	1 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 1 · High	6 Participants	5 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 1 · Blooming	3 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 2 · None	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 2 · Low	0 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 2 · Medium	8 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 2 · High	12 Participants	7 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 2: OPTISON Dose Level 2 · Blooming	2 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 1 · None	2 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 1 · Low	0 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 1 · Medium	9 Participants	3 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 1 · High	10 Participants	3 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 1 · Blooming	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 2 · None	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 2 · Low	1 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 2 · Medium	7 Participants	0 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 2 · High	14 Participants	7 Participants
Number of Participants by Degree of Left Ventricular Opacification (LVO) Assessed by Visual Peak Contrast Intensity Reader 3: OPTISON Dose Level 2 · Blooming	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Population: PP population consisted of all participants who had available non-contrast harmonic images and OPTISON-enhanced echocardiographic images, irrespective of the quality of CE-echo and who did not have an important protocol deviation impacting study primary endpoint. Here, "Number Analyzed" signifies participants who were evaluable for specified categories.

Peak LV contrast filling for LVO was categorized as: 0 = none (0 percent \[%\] filling); 1 = faint (around 33% filling); 2 = intermediate (around 67% filling); 3 = full (100% filling) and data were presented by readers (independent blinded) and dose levels.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=23 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=7 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 2 · Faint	0 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 2 · Intermediate	3 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 2 · Full	19 Participants	7 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 1 · None	2 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 1 · Faint	0 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 1 · Intermediate	2 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 1 · Full	18 Participants	6 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 2 · None	1 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 2 · Faint	0 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 2 · Intermediate	2 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 2: OPTISON Dose Level 2 · Full	20 Participants	7 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 1 · None	2 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 1 · Faint	0 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 1 · Intermediate	1 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 1 · Full	19 Participants	6 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 2 · None	1 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 2 · Faint	1 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 2 · Intermediate	1 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 3: OPTISON Dose Level 2 · Full	20 Participants	7 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 1 · None	2 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 1 · Faint	1 Participants	0 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 1 · Intermediate	1 Participants	1 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 1 · Full	18 Participants	5 Participants
Number of Participants by Grade of Left Ventricular Opacification (LVO) Assessed by Peak Left Ventricular (LV) Contrast Filling Reader 1: OPTISON Dose Level 2 · None	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Population: PP population consisted of all participants who had available non-contrast harmonic images and OPTISON-enhanced echocardiographic images, irrespective of the quality of CE-echo and who did not have an important protocol deviation impacting study primary endpoint. Here, "Number Analyzed" signifies participants who were evaluable for specified categories.

Contrast enhancement duration was determined from the time the contrast appeared in the LV to the time the contrast almost dissipated from the left chamber. 3 independent blinded reader performed evaluation.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=23 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=7 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · 0 minute	3 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · 1 minute (<1 minute contrast duration)	2 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · 2 minutes (1-2 minutes contrast duration)	5 Participants	3 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · 4 minutes (2-4 minutes contrast duration)	10 Participants	2 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · 7 minutes (4-7 minutes contrast duration)	2 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · 10 minutes (7-10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 1 · None of the above (>10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · 0 minute	2 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · 1 minute (<1 minute contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · 2 minutes (1-2 minutes contrast duration)	7 Participants	2 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · 4 minutes (2-4 minutes contrast duration)	10 Participants	4 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · 7 minutes (4-7 minutes contrast duration)	4 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · 10 minutes (7-10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 1: OPTISON Dose Level 2 · None of the above (>10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · 0 minute	2 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · 1 minute (<1 minute contrast duration)	0 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · 2 minutes (1-2 minutes contrast duration)	7 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · 4 minutes (2-4 minutes contrast duration)	11 Participants	3 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · 7 minutes (4-7 minutes contrast duration)	2 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · 10 minutes (7-10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 1 · None of the above (>10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · 0 minute	1 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · 1 minute (<1 minute contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · 2 minutes (1-2 minutes contrast duration)	3 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · 4 minutes (2-4 minutes contrast duration)	14 Participants	5 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · 7 minutes (4-7 minutes contrast duration)	5 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · 10 minutes (7-10 minutes contrast duration)	0 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 2: OPTISON Dose Level 2 · None of the above (>10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · 0 minute	3 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · 1 minute (<1 minute contrast duration)	2 Participants	2 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · 2 minutes (1-2 minutes contrast duration)	7 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · 4 minutes (2-4 minutes contrast duration)	10 Participants	3 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · 7 minutes (4-7 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · 10 minutes (7-10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 1 · None of the above (>10 minutes contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · 0 minute	2 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · 1 minute (<1 minute contrast duration)	0 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · 2 minutes (1-2 minutes contrast duration)	6 Participants	3 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · 4 minutes (2-4 minutes contrast duration)	14 Participants	3 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · 7 minutes (4-7 minutes contrast duration)	1 Participants	0 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · 10 minutes (7-10 minutes contrast duration)	0 Participants	1 Participants
Number of Participants by Contrast Enhancement Duration in the Left Ventricular (LV) Chamber Reader 3: OPTISON Dose Level 2 · None of the above (>10 minutes contrast duration)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Population: PP population consisted of all participants who had available non-contrast harmonic images and OPTISON-enhanced echocardiographic images, irrespective of the quality of CE-echo and who did not have an important protocol deviation impacting study primary endpoint. Each participants underwent an echocardiographic procedure first without contrast administration, then intravenous bolus injection of OPTISON. Here, "Number Analyzed" signifies participants who were evaluable for specified categories.

Diagnostic confidence for the assessment of LV EBD and wall motion was scored for non-contrast and OPTISON-enhanced echocardiographic acquisitions separately using a 4-point scale which ranged from ranged 0 to 4, where 0 = no confidence, 1 = low confidence, 2 = moderate confidence, 3 = high confidence. A higher score indicates better confidence level. Data were presented by reader (independent blinded), non-contrast and dose levels.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=23 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=7 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: Non-contrast · No confidence	10 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: Non-contrast · Low confidence	9 Participants	4 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: Non-contrast · Moderate confidence	4 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: Non-contrast · High confidence	0 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 1 · No confidence	3 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 1 · Low confidence	2 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 1 · Moderate confidence	9 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 1 · High confidence	8 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 2 · No confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 2 · Low confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 2 · Moderate confidence	11 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 1: OPTISON Dose Level 2 · High confidence	9 Participants	7 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: Non-contrast · No confidence	6 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: Non-contrast · Low confidence	15 Participants	6 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: Non-contrast · Moderate confidence	2 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: Non-contrast · High confidence	0 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 1 · No confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 1 · Low confidence	3 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 1 · Moderate confidence	7 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 1 · High confidence	10 Participants	4 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 2 · No confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 2 · Low confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 2 · Moderate confidence	10 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 2: OPTISON Dose Level 2 · High confidence	10 Participants	6 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: Non-contrast · No confidence	10 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: Non-contrast · Low confidence	7 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: Non-contrast · Moderate confidence	5 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: Non-contrast · High confidence	1 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 1 · No confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 1 · Low confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 1 · Moderate confidence	7 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 1 · High confidence	11 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 2 · No confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 2 · Low confidence	0 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 2 · Moderate confidence	11 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Endocardial Border Delineation (LV EBD) and Wall Motion for Contrast and Non-Contrast Enhanced Images Reader 3: OPTISON Dose Level 2 · High confidence	11 Participants	5 Participants

SECONDARY outcome

Timeframe: Images were captured during the study echocardiogram (0 to 30 minutes) on Day 1 and blinded image evaluations (BIE) were carried out at the study core laboratory following image transfer

Population: PP population consisted of all participants who had available non-contrast harmonic images and OPTISON-enhanced echocardiographic images, irrespective of the quality of CE-echo and who did not have an important protocol deviation impacting study primary endpoint. Each participants underwent an echocardiographic procedure first without contrast administration, then intravenous bolus injection of OPTISON. Here, "Number Analyzed" signifies participants who were evaluable for specified categories.

Diagnostic confidence for the evaluation of LVEF was calculated using the formula: (end diastole volume - end systole volume)/(end diastole volume) was scored for non-contrast and OPTISON-enhanced echocardiographic acquisitions separately using a 4-point scale which ranged from 0 to 3, where 0 = no confidence, 1 = low confidence, 2 = moderate confidence, 3 = high confidence. A higher score indicates better confidence level. Data were presented by reader (independent blinded), non-contrast and dose levels.

Outcome measures

Outcome measures
Measure	Body Weight Group >40 kg: OPTISON n=23 Participants Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level.	Body Weight Group <=40 kg: OPTISON n=7 Participants Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively.
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: Non-contrast · No confidence	11 Participants	4 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: Non-contrast · Low confidence	11 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: Non-contrast · Moderate confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: Non-contrast · High confidence	0 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 1 · No confidence	5 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 1 · Low confidence	1 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 1 · Moderate confidence	10 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 1 · High confidence	6 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 2 · No confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 2 · Low confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 2 · Moderate confidence	11 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 1: OPTISON Dose Level 2 · High confidence	9 Participants	7 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: Non-contrast · No confidence	16 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: Non-contrast · Low confidence	5 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: Non-contrast · Moderate confidence	2 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: Non-contrast · High confidence	0 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 1 · No confidence	4 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 1 · Low confidence	0 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 1 · Moderate confidence	10 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 1 · High confidence	8 Participants	4 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 2 · No confidence	2 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 2 · Low confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 2 · Moderate confidence	8 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 2: OPTISON Dose Level 2 · High confidence	12 Participants	6 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: Non-contrast · No confidence	17 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: Non-contrast · Low confidence	3 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: Non-contrast · Moderate confidence	3 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: Non-contrast · High confidence	0 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 1 · No confidence	4 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 1 · Low confidence	5 Participants	2 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 1 · Moderate confidence	7 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 1 · High confidence	6 Participants	3 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 2 · No confidence	7 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 2 · Low confidence	1 Participants	0 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 2 · Moderate confidence	6 Participants	1 Participants
Number of Participants by Diagnostic Confidence of Left Ventricular Ejection Fraction (LVEF) for Non-contrast and OPTISON Enhanced Echocardiography Reader 3: OPTISON Dose Level 2 · High confidence	9 Participants	5 Participants

Adverse Events

Body Weight Group <=40 kg: OPTISON

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Body Weight Group >40 kg: OPTISON

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

David Thompson, MD, PhD

GE HealthCare

Phone: +44 7775 543206

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI and/or institution is that the Sponsor can review results communications prior to public release and can restrict communications regarding trial results for a period that is more than 30 days (publications/abstracts) but not to exceed 90 days (patent related issues) from the time submitted to the Sponsor to review. The PI may be asked to remove any Sponsor confidential information and/or delay publication to protect any proprietary information.
Publication restrictions are in place

Restriction type: OTHER

Measure	Body Weight Group <=40 kg: OPTISON n=8 participants at risk Participants with body weight \>=20 to \<=28 kg received OPTISON 0.1 mL (dose level 1) or 0.2 mL (dose level 2); and participants with body weight \>28 to \<=40 kg received OPTISON 0.2 mL (dose level 1) or 0.3 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose for body weight \>=20 to \<=28 kg and \>28 to \<=40 kg was 1.0 mL and 1.5 mL per dose level, respectively. All subjects were imaged without contrast then with dose level 1 and then dose level 2. So it is impossible to separate the AE for each intervention.	Body Weight Group >40 kg: OPTISON n=29 participants at risk Participants with body weight \>40 kg received OPTISON 0.2 (dose level 1) or 0.4 mL (dose level 2) IV injection, 10 minutes apart on Day 1. The maximum allowed cumulative dose was 1.8 mL per dose level. All subjects were imaged without contrast then with dose level 1 and then dose level 2. So it is impossible to separate the AE for each intervention.
Cardiac disorders Supraventricular extrasystoles	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	3.4% 1/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	3.4% 1/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	6.9% 2/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	6.9% 2/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Gastrointestinal disorders Nausea	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	6.9% 2/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Gastrointestinal disorders Vomiting	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	0.00% 0/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
General disorders Injection site pain	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	0.00% 0/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Injury, poisoning and procedural complications Clavicle fracture	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	0.00% 0/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Nervous system disorders Dizziness	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	6.9% 2/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Nervous system disorders Dysgeusia	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	3.4% 1/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Nervous system disorders Headache	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	10.3% 3/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Nervous system disorders Migraine	0.00% 0/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	3.4% 1/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Nervous system disorders Taste disorder	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	3.4% 1/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Psychiatric disorders Mood swings	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	0.00% 0/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.
Respiratory, thoracic and mediastinal disorders Cough	12.5% 1/8 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.	0.00% 0/29 • 0- 72 hours The Safety population consisted of all enrolled participants who received \>=1 dose of OPTISON in the study.