Cardiac Disease
Conditions
Keywords
Echo, Echocardiogram, Cardiac ultrasound, suboptimal, contrast agent, enhancing agent, LVO, LVEBD
Brief summary
NH002 (Perflutren Lipid Microspheres) Injectable Suspension is an ultrasound contrast agent for use in patients with suboptimal echocardiograms to opacify the left ventricular (LV) chamber and to improve the delineation of the LV endocardial border. The primary objective of this study is to evaluate the safety and tolerability of 3 ascending doses of NH002.
Interventions
NH002 is formulated as a microbubble injectable suspension for intravenous administration. NH002 requires an activation process prior to use.
DIAGNOSTIC_TESTEchocardiogram
Each patient will undergo an unenhanced ultrasound examination and a NH002 contrast-enhanced examination on the same day.
Sponsors
StatPlus,Inc.
Trust Bio-sonics, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Masking description
The reviewer of echocardiograms in this trial is blinded to the treatment assignments and subject identifiers.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Male or female subjects 20 years of age or older 2. Ability to understand and the willingness to provide written informed consent 3. Suspected of having cardiac disease or undergoing evaluation of cardiac anatomy for congenital heart disease 4. Negative pregnancy test within 24 hours of the procedure if subject is a woman of childbearing potential
Exclusion criteria
1. Known right-to-left, bidirectional, or transient right-to-left cardiac shunt(s) 2. Chronic obstructive pulmonary disease 3. Ejection fraction at screening or baseline \<40% 4. Uncontrolled serious ventricular arrhythmias or at high risk for arrhythmias due to prolongation of the QT interval (QT corrected by Fridericia's formula \>450 msec in males and \>470 msec in females) 5. Clinically significant abnormality in renal and liver function tests (alanine aminotransferase/aspartate aminotransferase \>2 × upper limit of normal \[ULN\]; serum creatinine \> 1.5 × ULN) 6. Known or suspected hypersensitivity to one or more of the ingredients of NH002, perflutren, or other echocardiographic contrast agent 7. Received an investigational compound within 30 days before enrolling in the study 8. Received any contrast agent either intravascularly or orally within 48 hours before NH002 administration 9. Pregnant or lactating female (conception during the study should be avoided) 10. Serious medical or psychiatric illness/condition likely, in the judgment of the investigator, to interfere with compliance to protocol treatment/research 11. Clinically unstable cardiopulmonary conditions considered not suitable for participation in the trial, in the judgment of the investigator 12. Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥ 110 mmHg) or arterial hypotension (defined as systolic blood pressure ≤ 90 mmHg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Troponin T | pre-injection and 240 minutes post-injection | Monitor for any changes in Cardiac troponin T |
| Cardiac Troponin I | pre-injection and 240 minutes post-injection | Monitor for any changes in Cardiac troponin I |
| Oxygen Saturation by Pulse Oximetry (SpO2) | From pre-injection to 120 minutes post-injection | Monitor for any changes in SpO2 |
| Rate of Any Potential Adverse Allergic Reaction | From pre-injection to 240 minutes post-injection | Monitor for any potential adverse allergic reaction |
| 12-lead ECGs | From pre-injection to 60 minutes post injection | Standard 12-lead ECGs will be assessed from pre-injection to 60 minutes post-injection for changes in QT/ corrected QT(QTc) interval (in ms) and ECG morphology; each standard 12-lead ECG assessment will be scored as either normal or abnormal |
| Body Temperature | From pre-injection to 120 minutes post injection | Monitor for any changes in body temperature (in Celsius degree) |
| Heart Rate | From pre-injection to 120 minutes post injection | Monitor for any changes in heart rate (in beats/min) |
| Respiratory Rate | From pre-injection to 120 minutes post injection | Monitor for any changes in respiratory rate (in breaths/min) |
| Blood Pressure | From pre-injection to 120 minutes post injection | Monitor for any changes in blood pressure (in mmHg) |
| Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | From pre-injection to 240 minutes post-injection | Monitor for any changes in TT and aPTT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Endocardial Border Delineation (LVEBD) | Image data obtained pre-injection and within 10 minutes post-injection | The change from baseline on the left ventricular endocardial border delineation (LVEBD) score, defined using a standard 12-segment model, as assessed by the blinded central reader(s). The left ventricular (LV) endocardium of the 4- or 2- chamber apical views are divided into 6 segments, with 2 basal, mid- and apical segments in each view. For each segment, LVEBD is graded as follows: 0= inadequate border (border not visible); 1= sufficient (border barely visible); 2= good (border clearly visible). A total delineation score (0-24) is obtained by adding the scores from the 6 individual segments in each of the 2 views. The changes from baseline on LVEBD score of subjects with suboptimal LVEBD at baseline, as defined by 2 or more contiguous segments of 6 segments that cannot be visualized reliably in either the apical 4 and/or the 2-chamber view, as assessed by the blinded central reader(s) |
| Duration of Clinically Useful Contrast | Image data obtained pre-injection and within 10 minutes post-injection | A duration of clinically useful contrast calculated by measuring the time between the disappearance of shadowing effect (useful effect starts) and the time when moderate or full LV enhancement and contrast enhancement are no longer adequate (useful effect ends), as assessed by the blinded central reader(s) |
| Left Ventricular Opacification (LVO) | Image data obtained pre-injection and within 10 minutes post-injection | The percentage of subjects with moderate or complete left ventricular opacification (LVO), defined by an LVO grade of 2 (moderate) or 3 (complete), as assessed by the blinded central reader(s). The percentage of subjects with complete LVO, defined by an LVO grade of 3 (complete), as assessed by the blinded central reader(s) |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants received single intravenous bolus injection dose of NH002 2.5 µl/kg. | 12 |
| Cohort 2 Participants received single intravenous bolus injection dose of NH002 5.0 µl/kg. | 12 |
| Cohort 3 Participants received single intravenous bolus injection dose of NH002 10.0 µl/kg. | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | Total | Cohort 3 | Cohort 2 | Cohort 1 |
|---|---|---|---|---|
| Age, Continuous | 39.7 years STANDARD_DEVIATION 12.29 | 36.8 years STANDARD_DEVIATION 11.42 | 38.8 years STANDARD_DEVIATION 10.29 | 43.5 years STANDARD_DEVIATION 14.77 |
| Height | 166.28 centimeter STANDARD_DEVIATION 11.29 | 166.74 centimeter STANDARD_DEVIATION 11.991 | 163.7 centimeter STANDARD_DEVIATION 10.93 | 168.4 centimeter STANDARD_DEVIATION 11.396 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 12 Participants | 12 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 17 Participants | 6 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 19 Participants | 6 Participants | 5 Participants | 8 Participants |
| Weight | 71.21 kilogram STANDARD_DEVIATION 19.933 | 73.59 kilogram STANDARD_DEVIATION 22.279 | 63.17 kilogram STANDARD_DEVIATION 13.131 | 76.88 kilogram STANDARD_DEVIATION 21.992 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 2 / 12 | 7 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
12-lead ECGs
Standard 12-lead ECGs will be assessed from pre-injection to 60 minutes post-injection for changes in QT/ corrected QT(QTc) interval (in ms) and ECG morphology; each standard 12-lead ECG assessment will be scored as either normal or abnormal
Time frame: From pre-injection to 60 minutes post injection
Population: All abnormal findings of 12-lead ECG interpretations after dosing were assessed as non-clinically significant and not related to NH002.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | 12-lead ECGs | Baseline (QT) | 393.9 millisecond | Standard Deviation 19.37 |
| Cohort 1 | 12-lead ECGs | Change of Baseline (QT) at 10 minutes post-dose | 2.8 millisecond | Standard Deviation 13.65 |
| Cohort 1 | 12-lead ECGs | Change of Baseline (QT) at 30 minutes post-dose | 10.8 millisecond | Standard Deviation 13.28 |
| Cohort 1 | 12-lead ECGs | Change of Baseline (QT) at 60 minutes post-dose | 7.1 millisecond | Standard Deviation 17.17 |
| Cohort 1 | 12-lead ECGs | Baseline (QTc) | 415.1 millisecond | Standard Deviation 21.71 |
| Cohort 1 | 12-lead ECGs | Change of baseline (QTc) at 10 minutes post-dose | 1.3 millisecond | Standard Deviation 13.92 |
| Cohort 1 | 12-lead ECGs | Change of baseline (QTc) at 30 minutes post-dose | 0.4 millisecond | Standard Deviation 14.25 |
| Cohort 1 | 12-lead ECGs | Change of baseline (QTc) at 60 minutes post-dose | -0.1 millisecond | Standard Deviation 13.03 |
| Cohort 2 | 12-lead ECGs | Change of Baseline (QT) at 30 minutes post-dose | 6.0 millisecond | Standard Deviation 12.59 |
| Cohort 2 | 12-lead ECGs | Change of baseline (QTc) at 30 minutes post-dose | -1.3 millisecond | Standard Deviation 12.14 |
| Cohort 2 | 12-lead ECGs | Change of Baseline (QT) at 60 minutes post-dose | 3.4 millisecond | Standard Deviation 17.17 |
| Cohort 2 | 12-lead ECGs | Baseline (QTc) | 415.9 millisecond | Standard Deviation 20.38 |
| Cohort 2 | 12-lead ECGs | Change of baseline (QTc) at 10 minutes post-dose | -6.4 millisecond | Standard Deviation 10.95 |
| Cohort 2 | 12-lead ECGs | Baseline (QT) | 392.0 millisecond | Standard Deviation 24.07 |
| Cohort 2 | 12-lead ECGs | Change of Baseline (QT) at 10 minutes post-dose | -6.0 millisecond | Standard Deviation 13.16 |
| Cohort 2 | 12-lead ECGs | Change of baseline (QTc) at 60 minutes post-dose | -3.0 millisecond | Standard Deviation 11.96 |
| Cohort 3 | 12-lead ECGs | Change of Baseline (QT) at 30 minutes post-dose | 16.0 millisecond | Standard Deviation 13.4 |
| Cohort 3 | 12-lead ECGs | Change of Baseline (QT) at 10 minutes post-dose | 6.8 millisecond | Standard Deviation 17.65 |
| Cohort 3 | 12-lead ECGs | Baseline (QT) | 386.3 millisecond | Standard Deviation 25.99 |
| Cohort 3 | 12-lead ECGs | Change of Baseline (QT) at 60 minutes post-dose | 10.6 millisecond | Standard Deviation 9.59 |
| Cohort 3 | 12-lead ECGs | Change of baseline (QTc) at 30 minutes post-dose | 8.8 millisecond | Standard Deviation 9.17 |
| Cohort 3 | 12-lead ECGs | Change of baseline (QTc) at 10 minutes post-dose | 7.8 millisecond | Standard Deviation 7.7 |
| Cohort 3 | 12-lead ECGs | Baseline (QTc) | 404.6 millisecond | Standard Deviation 15.32 |
| Cohort 3 | 12-lead ECGs | Change of baseline (QTc) at 60 minutes post-dose | 6.9 millisecond | Standard Deviation 5.88 |
Primary
Blood Pressure
Monitor for any changes in blood pressure (in mmHg)
Time frame: From pre-injection to 120 minutes post injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Blood Pressure | Change from baseline (SBP) at 10 minutes post-dose | -2.5 mmHg | Standard Deviation 9.48 |
| Cohort 1 | Blood Pressure | Change from baseline (DBP) at 10 minutes post-dose | -2.6 mmHg | Standard Deviation 6.56 |
| Cohort 1 | Blood Pressure | Change from baseline (DBP) at 30 minutes post-dose | -3.9 mmHg | Standard Deviation 8.12 |
| Cohort 1 | Blood Pressure | Change from baseline (DBP) at 120 minutes post-dose | -2.3 mmHg | Standard Deviation 7.94 |
| Cohort 1 | Blood Pressure | Change from baseline (DBP) at 60 minutes post-dose | -3.0 mmHg | Standard Deviation 10.4 |
| Cohort 1 | Blood Pressure | Baseline (DBP) | 85.2 mmHg | Standard Deviation 11.61 |
| Cohort 1 | Blood Pressure | Change from baseline (SBP) at 30 minutes post-dose | -5.2 mmHg | Standard Deviation 11.54 |
| Cohort 1 | Blood Pressure | Baseline (SBP) | 132.8 mmHg | Standard Deviation 14.93 |
| Cohort 1 | Blood Pressure | Change from baseline (SBP) at 60 minutes post-dose | -4.8 mmHg | Standard Deviation 15.03 |
| Cohort 1 | Blood Pressure | Change from baseline (SBP) at 120 minutes post-dose | -4.0 mmHg | Standard Deviation 13.1 |
| Cohort 2 | Blood Pressure | Baseline (DBP) | 68.5 mmHg | Standard Deviation 13.3 |
| Cohort 2 | Blood Pressure | Change from baseline (SBP) at 30 minutes post-dose | 4.8 mmHg | Standard Deviation 13.33 |
| Cohort 2 | Blood Pressure | Change from baseline (DBP) at 10 minutes post-dose | 0 mmHg | Standard Deviation 4.92 |
| Cohort 2 | Blood Pressure | Change from baseline (SBP) at 10 minutes post-dose | 0.5 mmHg | Standard Deviation 6.45 |
| Cohort 2 | Blood Pressure | Change from baseline (SBP) at 120 minutes post-dose | 7.6 mmHg | Standard Deviation 15.47 |
| Cohort 2 | Blood Pressure | Change from baseline (DBP) at 30 minutes post-dose | 4.1 mmHg | Standard Deviation 10.66 |
| Cohort 2 | Blood Pressure | Change from baseline (DBP) at 120 minutes post-dose | 6.8 mmHg | Standard Deviation 14.16 |
| Cohort 2 | Blood Pressure | Change from baseline (SBP) at 60 minutes post-dose | 1.5 mmHg | Standard Deviation 12.59 |
| Cohort 2 | Blood Pressure | Change from baseline (DBP) at 60 minutes post-dose | 3.6 mmHg | Standard Deviation 11.52 |
| Cohort 2 | Blood Pressure | Baseline (SBP) | 106.8 mmHg | Standard Deviation 15.6 |
| Cohort 3 | Blood Pressure | Change from baseline (DBP) at 60 minutes post-dose | 7.8 mmHg | Standard Deviation 11.58 |
| Cohort 3 | Blood Pressure | Change from baseline (DBP) at 120 minutes post-dose | 8.7 mmHg | Standard Deviation 14.5 |
| Cohort 3 | Blood Pressure | Baseline (SBP) | 112.7 mmHg | Standard Deviation 16.33 |
| Cohort 3 | Blood Pressure | Change from baseline (SBP) at 10 minutes post-dose | -0.3 mmHg | Standard Deviation 7.76 |
| Cohort 3 | Blood Pressure | Change from baseline (SBP) at 30 minutes post-dose | 4.1 mmHg | Standard Deviation 9.46 |
| Cohort 3 | Blood Pressure | Change from baseline (SBP) at 60 minutes post-dose | 6.0 mmHg | Standard Deviation 10.44 |
| Cohort 3 | Blood Pressure | Change from baseline (SBP) at 120 minutes post-dose | 13.8 mmHg | Standard Deviation 19.6 |
| Cohort 3 | Blood Pressure | Baseline (DBP) | 71.5 mmHg | Standard Deviation 11.76 |
| Cohort 3 | Blood Pressure | Change from baseline (DBP) at 10 minutes post-dose | 2.6 mmHg | Standard Deviation 5.96 |
| Cohort 3 | Blood Pressure | Change from baseline (DBP) at 30 minutes post-dose | 3.1 mmHg | Standard Deviation 9.6 |
Primary
Body Temperature
Monitor for any changes in body temperature (in Celsius degree)
Time frame: From pre-injection to 120 minutes post injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Body Temperature | Baseline | 36.76 Celsius degree | Standard Deviation 0.294 |
| Cohort 1 | Body Temperature | Change from baseline at 5 minutes post-dose | -0.01 Celsius degree | Standard Deviation 0.215 |
| Cohort 1 | Body Temperature | Change from baseline at 10 minutes post-dose | -0.01 Celsius degree | Standard Deviation 0.312 |
| Cohort 1 | Body Temperature | Change from baseline at 30 minutes post-dose | -0.07 Celsius degree | Standard Deviation 0.328 |
| Cohort 1 | Body Temperature | Change from baseline at 60 minutes post-dose | -0.08 Celsius degree | Standard Deviation 0.457 |
| Cohort 1 | Body Temperature | Change from baseline at 120 minutes post-dose | -0.07 Celsius degree | Standard Deviation 0.442 |
| Cohort 2 | Body Temperature | Change from baseline at 120 minutes post-dose | 0.1 Celsius degree | Standard Deviation 0.283 |
| Cohort 2 | Body Temperature | Baseline | 36.73 Celsius degree | Standard Deviation 0.306 |
| Cohort 2 | Body Temperature | Change from baseline at 30 minutes post-dose | 0.11 Celsius degree | Standard Deviation 0.215 |
| Cohort 2 | Body Temperature | Change from baseline at 60 minutes post-dose | 0.05 Celsius degree | Standard Deviation 0.271 |
| Cohort 2 | Body Temperature | Change from baseline at 5 minutes post-dose | -0.02 Celsius degree | Standard Deviation 0.195 |
| Cohort 2 | Body Temperature | Change from baseline at 10 minutes post-dose | 0.07 Celsius degree | Standard Deviation 0.235 |
| Cohort 3 | Body Temperature | Change from baseline at 5 minutes post-dose | -0.01 Celsius degree | Standard Deviation 0.268 |
| Cohort 3 | Body Temperature | Change from baseline at 10 minutes post-dose | -0.06 Celsius degree | Standard Deviation 0.207 |
| Cohort 3 | Body Temperature | Change from baseline at 120 minutes post-dose | -0.02 Celsius degree | Standard Deviation 0.518 |
| Cohort 3 | Body Temperature | Change from baseline at 30 minutes post-dose | 0 Celsius degree | Standard Deviation 0.2 |
| Cohort 3 | Body Temperature | Baseline | 36.76 Celsius degree | Standard Deviation 0.385 |
| Cohort 3 | Body Temperature | Change from baseline at 60 minutes post-dose | -0.18 Celsius degree | Standard Deviation 0.313 |
Primary
Cardiac Troponin I
Monitor for any changes in Cardiac troponin I
Time frame: pre-injection and 240 minutes post-injection
Population: Troponin I was utilized at site 102. The sample sizes were 5, 7, and 7 for cohorts 1, 2, and 3, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cardiac Troponin I | 240 minutes after dosing (troponin I) | 0.005 ng/mL | Standard Deviation 0 |
| Cohort 1 | Cardiac Troponin I | Baseline (troponin I) | 0.005 ng/mL | Standard Deviation 0 |
| Cohort 1 | Cardiac Troponin I | Change from baseline (troponin I) at 240 minutes post-dose | 0.000 ng/mL | Standard Deviation 0 |
| Cohort 2 | Cardiac Troponin I | 240 minutes after dosing (troponin I) | 0.005 ng/mL | Standard Deviation 0 |
| Cohort 2 | Cardiac Troponin I | Baseline (troponin I) | 0.005 ng/mL | Standard Deviation 0 |
| Cohort 2 | Cardiac Troponin I | Change from baseline (troponin I) at 240 minutes post-dose | 0.000 ng/mL | Standard Deviation 0 |
| Cohort 3 | Cardiac Troponin I | Baseline (troponin I) | 0.005 ng/mL | Standard Deviation 0 |
| Cohort 3 | Cardiac Troponin I | Change from baseline (troponin I) at 240 minutes post-dose | 0.000 ng/mL | Standard Deviation 0 |
| Cohort 3 | Cardiac Troponin I | 240 minutes after dosing (troponin I) | 0.005 ng/mL | Standard Deviation 0 |
Primary
Cardiac Troponin T
Monitor for any changes in Cardiac troponin T
Time frame: pre-injection and 240 minutes post-injection
Population: Troponin T was utilized at site 101. The sample sizes were 7, 5, and 5 for cohorts 1, 2, and 3, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cardiac Troponin T | Change from baseline (troponin T) at 240 minutes post-dose | 1.14 ng/L | Standard Deviation 1.878 |
| Cohort 1 | Cardiac Troponin T | 240 minutes after dosing (troponin T) | 5.21 ng/L | Standard Deviation 1.368 |
| Cohort 1 | Cardiac Troponin T | Baseline (troponin T) | 4.07 ng/L | Standard Deviation 2.53 |
| Cohort 2 | Cardiac Troponin T | Change from baseline (troponin T) at 240 minutes post-dose | 0.8 ng/L | Standard Deviation 1.105 |
| Cohort 2 | Cardiac Troponin T | 240 minutes after dosing (troponin T) | 2.3 ng/L | Standard Deviation 1.105 |
| Cohort 2 | Cardiac Troponin T | Baseline (troponin T) | 1.5 ng/L | Standard Deviation 0 |
| Cohort 3 | Cardiac Troponin T | 240 minutes after dosing (troponin T) | 5.72 ng/L | Standard Deviation 4.387 |
| Cohort 3 | Cardiac Troponin T | Baseline (troponin T) | 4.38 ng/L | Standard Deviation 1.824 |
| Cohort 3 | Cardiac Troponin T | Change from baseline (troponin T) at 240 minutes post-dose | 1.34 ng/L | Standard Deviation 3.833 |
Primary
Heart Rate
Monitor for any changes in heart rate (in beats/min)
Time frame: From pre-injection to 120 minutes post injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Heart Rate | Change from baseline at 120 minutes post-dose | 4.9 beats/minute | Standard Deviation 10.29 |
| Cohort 1 | Heart Rate | Change from baseline at 30 minutes post-dose | -3.0 beats/minute | Standard Deviation 5.34 |
| Cohort 1 | Heart Rate | Baseline | 70.1 beats/minute | Standard Deviation 9.93 |
| Cohort 1 | Heart Rate | Change from baseline at 10 minutes post-dose | -0.7 beats/minute | Standard Deviation 2.71 |
| Cohort 1 | Heart Rate | Change from baseline at 60 minutes post-dose | -0.9 beats/minute | Standard Deviation 5.96 |
| Cohort 2 | Heart Rate | Change from baseline at 10 minutes post-dose | -0.1 beats/minute | Standard Deviation 5.87 |
| Cohort 2 | Heart Rate | Change from baseline at 120 minutes post-dose | 6.8 beats/minute | Standard Deviation 12.4 |
| Cohort 2 | Heart Rate | Change from baseline at 60 minutes post-dose | -1.2 beats/minute | Standard Deviation 4.37 |
| Cohort 2 | Heart Rate | Change from baseline at 30 minutes post-dose | -1.3 beats/minute | Standard Deviation 5.99 |
| Cohort 2 | Heart Rate | Baseline | 71.3 beats/minute | Standard Deviation 7.73 |
| Cohort 3 | Heart Rate | Change from baseline at 120 minutes post-dose | 8.3 beats/minute | Standard Deviation 9.9 |
| Cohort 3 | Heart Rate | Baseline | 69.0 beats/minute | Standard Deviation 8.06 |
| Cohort 3 | Heart Rate | Change from baseline at 30 minutes post-dose | -0.3 beats/minute | Standard Deviation 6.85 |
| Cohort 3 | Heart Rate | Change from baseline at 60 minutes post-dose | 0.7 beats/minute | Standard Deviation 4.56 |
| Cohort 3 | Heart Rate | Change from baseline at 10 minutes post-dose | -0.1 beats/minute | Standard Deviation 3.73 |
Primary
Oxygen Saturation by Pulse Oximetry (SpO2)
Monitor for any changes in SpO2
Time frame: From pre-injection to 120 minutes post-injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 60 minutes post-dose | 0.5 percentage | Standard Deviation 1.88 |
| Cohort 1 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 30 minutes post-dose | 0.2 percentage | Standard Deviation 1.27 |
| Cohort 1 | Oxygen Saturation by Pulse Oximetry (SpO2) | Baseline | 98.8 percentage | Standard Deviation 1.06 |
| Cohort 1 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 10 minutes post-dose | 0.4 percentage | Standard Deviation 1.31 |
| Cohort 1 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 120 minutes post-dose | 0 percentage | Standard Deviation 1.13 |
| Cohort 2 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 30 minutes post-dose | 0.3 percentage | Standard Deviation 1.29 |
| Cohort 2 | Oxygen Saturation by Pulse Oximetry (SpO2) | Baseline | 98.9 percentage | Standard Deviation 1.51 |
| Cohort 2 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 10 minutes post-dose | 0.3 percentage | Standard Deviation 0.62 |
| Cohort 2 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 60 minutes post-dose | 0.4 percentage | Standard Deviation 1.38 |
| Cohort 2 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 120 minutes post-dose | -0.2 percentage | Standard Deviation 1.64 |
| Cohort 3 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 120 minutes post-dose | 0.2 percentage | Standard Deviation 0.94 |
| Cohort 3 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 60 minutes post-dose | 0.8 percentage | Standard Deviation 1.22 |
| Cohort 3 | Oxygen Saturation by Pulse Oximetry (SpO2) | Baseline | 98.3 percentage | Standard Deviation 1.14 |
| Cohort 3 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 30 minutes post-dose | -0.3 percentage | Standard Deviation 0.87 |
| Cohort 3 | Oxygen Saturation by Pulse Oximetry (SpO2) | Change from baseline at 10 minutes post-dose | -0.4 percentage | Standard Deviation 1.38 |
Primary
Rate of Any Potential Adverse Allergic Reaction
Monitor for any potential adverse allergic reaction
Time frame: From pre-injection to 240 minutes post-injection
Population: One subject allergic to the tap (not injection site) at 120 minutes after dosing. It was determined that there was no relationship between the data and the IP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Rate of Any Potential Adverse Allergic Reaction | 0 Participants |
| Cohort 2 | Rate of Any Potential Adverse Allergic Reaction | 0 Participants |
| Cohort 3 | Rate of Any Potential Adverse Allergic Reaction | 0 Participants |
Primary
Respiratory Rate
Monitor for any changes in respiratory rate (in breaths/min)
Time frame: From pre-injection to 120 minutes post injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Respiratory Rate | Change from baseline at 60 minutes post-dose | 0.5 breaths/minute | Standard Deviation 3.85 |
| Cohort 1 | Respiratory Rate | Change from baseline at 30 minutes post-dose | 0.9 breaths/minute | Standard Deviation 3.09 |
| Cohort 1 | Respiratory Rate | Baseline | 15.6 breaths/minute | Standard Deviation 3.55 |
| Cohort 1 | Respiratory Rate | Change from baseline at 10 minutes post-dose | 0.6 breaths/minute | Standard Deviation 3.8 |
| Cohort 1 | Respiratory Rate | Change from baseline at 120 minutes post-dose | 0.8 breaths/minute | Standard Deviation 3.43 |
| Cohort 2 | Respiratory Rate | Change from baseline at 30 minutes post-dose | -0.8 breaths/minute | Standard Deviation 3.28 |
| Cohort 2 | Respiratory Rate | Baseline | 15.1 breaths/minute | Standard Deviation 2.07 |
| Cohort 2 | Respiratory Rate | Change from baseline at 10 minutes post-dose | -0.6 breaths/minute | Standard Deviation 3.29 |
| Cohort 2 | Respiratory Rate | Change from baseline at 60 minutes post-dose | -0.9 breaths/minute | Standard Deviation 2.75 |
| Cohort 2 | Respiratory Rate | Change from baseline at 120 minutes post-dose | -0.5 breaths/minute | Standard Deviation 3.61 |
| Cohort 3 | Respiratory Rate | Change from baseline at 120 minutes post-dose | -1.3 breaths/minute | Standard Deviation 4.48 |
| Cohort 3 | Respiratory Rate | Change from baseline at 60 minutes post-dose | -2.3 breaths/minute | Standard Deviation 4.09 |
| Cohort 3 | Respiratory Rate | Baseline | 16.9 breaths/minute | Standard Deviation 4.44 |
| Cohort 3 | Respiratory Rate | Change from baseline at 30 minutes post-dose | -1.3 breaths/minute | Standard Deviation 4.71 |
| Cohort 3 | Respiratory Rate | Change from baseline at 10 minutes post-dose | -1.4 breaths/minute | Standard Deviation 3.12 |
Primary
Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT)
Monitor for any changes in TT and aPTT
Time frame: From pre-injection to 240 minutes post-injection
Population: The total number of subjects in cohort 2 who underwent TT testing was 11.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Baseline (TT) | 18.6 seconds | Standard Deviation 3.145 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 60 minutes post-dose | 0.22 seconds | Standard Deviation 0.395 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 120 minutes post-dose | 0.06 seconds | Standard Deviation 0.528 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 240 minutes post-dose | 0.11 seconds | Standard Deviation 0.497 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Baseline (APTT) | 31.54 seconds | Standard Deviation 3.888 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 60 minutes post-dose | -0.3 seconds | Standard Deviation 2.625 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 120 minutes post-dose | -0.49 seconds | Standard Deviation 3.11 |
| Cohort 1 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 240 minutes post-dose | -0.55 seconds | Standard Deviation 3.191 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 120 minutes post-dose | 0.05 seconds | Standard Deviation 0.95 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 120 minutes post-dose | -0.48 seconds | Standard Deviation 1.788 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 240 minutes post-dose | -0.05 seconds | Standard Deviation 0.62 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Baseline (APTT) | 28.76 seconds | Standard Deviation 27.81 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 60 minutes post-dose | -1.05 seconds | Standard Deviation 2.184 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Baseline (TT) | 17.81 seconds | Standard Deviation 0.667 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 60 minutes post-dose | -0.12 seconds | Standard Deviation 0.387 |
| Cohort 2 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 240 minutes post-dose | -0.68 seconds | Standard Deviation 1.516 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 120 minutes post-dose | -0.3 seconds | Standard Deviation 0.662 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 60 minutes post-dose | -0.24 seconds | Standard Deviation 0.724 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Baseline (TT) | 16.7 seconds | Standard Deviation 1.836 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (TT) at 240 minutes post-dose | 0.31 seconds | Standard Deviation 1.274 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 120 minutes post-dose | -0.61 seconds | Standard Deviation 2.586 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 60 minutes post-dose | -0.8 seconds | Standard Deviation 2.921 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Baseline (APTT) | 28.87 seconds | Standard Deviation 2.796 |
| Cohort 3 | Thrombin Time (TT) and Activated Partial Thromboplastin Time (aPTT) | Change from baseline (APTT) at 240 minutes post-dose | -1.5 seconds | Standard Deviation 2.375 |
Secondary
Duration of Clinically Useful Contrast
A duration of clinically useful contrast calculated by measuring the time between the disappearance of shadowing effect (useful effect starts) and the time when moderate or full LV enhancement and contrast enhancement are no longer adequate (useful effect ends), as assessed by the blinded central reader(s)
Time frame: Image data obtained pre-injection and within 10 minutes post-injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Duration of Clinically Useful Contrast | 7.2 minutes | Standard Deviation 2.458 |
| Cohort 2 | Duration of Clinically Useful Contrast | 7.67 minutes | Standard Deviation 1.684 |
| Cohort 3 | Duration of Clinically Useful Contrast | 3.59 minutes | Standard Deviation 1.854 |
Secondary
Left Ventricular Endocardial Border Delineation (LVEBD)
The change from baseline on the left ventricular endocardial border delineation (LVEBD) score, defined using a standard 12-segment model, as assessed by the blinded central reader(s). The left ventricular (LV) endocardium of the 4- or 2- chamber apical views are divided into 6 segments, with 2 basal, mid- and apical segments in each view. For each segment, LVEBD is graded as follows: 0= inadequate border (border not visible); 1= sufficient (border barely visible); 2= good (border clearly visible). A total delineation score (0-24) is obtained by adding the scores from the 6 individual segments in each of the 2 views. The changes from baseline on LVEBD score of subjects with suboptimal LVEBD at baseline, as defined by 2 or more contiguous segments of 6 segments that cannot be visualized reliably in either the apical 4 and/or the 2-chamber view, as assessed by the blinded central reader(s)
Time frame: Image data obtained pre-injection and within 10 minutes post-injection
Population: There were 9, 10, and 9 subjects with suboptimal baseline values in cohorts 1, 2, and 3, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Post-dose (subjects with suboptimal LVEBD at baseline) | 22.7 score on a scale | Standard Deviation 4 |
| Cohort 1 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Post-dose (all subjects) | 23.0 score on a scale | Standard Deviation 3.46 |
| Cohort 1 | Left Ventricular Endocardial Border Delineation (LVEBD) | Change from baseline (subjects with suboptimal LVEBD at baseline) | 14.1 score on a scale | Standard Deviation 6.11 |
| Cohort 1 | Left Ventricular Endocardial Border Delineation (LVEBD) | Change from baseline (all subjects) | 11.5 score on a scale | Standard Deviation 7.22 |
| Cohort 1 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Baseline (all subjects) | 11.5 score on a scale | Standard Deviation 6.75 |
| Cohort 1 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Baseline (subjects with suboptimal LVEBD at baseline) | 8.6 score on a scale | Standard Deviation 4.48 |
| Cohort 2 | Left Ventricular Endocardial Border Delineation (LVEBD) | Change from baseline (all subjects) | 14.8 score on a scale | Standard Deviation 4.71 |
| Cohort 2 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Baseline (all subjects) | 8.9 score on a scale | Standard Deviation 4.89 |
| Cohort 2 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Post-dose (subjects with suboptimal LVEBD at baseline) | 23.7 score on a scale | Standard Deviation 0.67 |
| Cohort 2 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Baseline (subjects with suboptimal LVEBD at baseline) | 7.4 score on a scale | Standard Deviation 3.72 |
| Cohort 2 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Post-dose (all subjects) | 23.8 score on a scale | Standard Deviation 0.62 |
| Cohort 2 | Left Ventricular Endocardial Border Delineation (LVEBD) | Change from baseline (subjects with suboptimal LVEBD at baseline) | 16.3 score on a scale | Standard Deviation 3.56 |
| Cohort 3 | Left Ventricular Endocardial Border Delineation (LVEBD) | Change from baseline (subjects with suboptimal LVEBD at baseline) | 16.1 score on a scale | Standard Deviation 6.57 |
| Cohort 3 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Post-dose (subjects with suboptimal LVEBD at baseline) | 23.9 score on a scale | Standard Deviation 0.33 |
| Cohort 3 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Baseline (all subjects) | 9.7 score on a scale | Standard Deviation 6.68 |
| Cohort 3 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Post-dose (all subjects) | 23.9 score on a scale | Standard Deviation 0.29 |
| Cohort 3 | Left Ventricular Endocardial Border Delineation (LVEBD) | Change from baseline (all subjects) | 14.3 score on a scale | Standard Deviation 6.59 |
| Cohort 3 | Left Ventricular Endocardial Border Delineation (LVEBD) | LVEBD scores_Baseline (subjects with suboptimal LVEBD at baseline) | 7.8 score on a scale | Standard Deviation 6.65 |
Secondary
Left Ventricular Opacification (LVO)
The percentage of subjects with moderate or complete left ventricular opacification (LVO), defined by an LVO grade of 2 (moderate) or 3 (complete), as assessed by the blinded central reader(s). The percentage of subjects with complete LVO, defined by an LVO grade of 3 (complete), as assessed by the blinded central reader(s)
Time frame: Image data obtained pre-injection and within 10 minutes post-injection
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Left Ventricular Opacification (LVO) | LVO grade of 2 (moderate) or 3 (complete) | 12 Participants |
| Cohort 1 | Left Ventricular Opacification (LVO) | LVO grade of 3 (complete) | 11 Participants |
| Cohort 2 | Left Ventricular Opacification (LVO) | LVO grade of 2 (moderate) or 3 (complete) | 12 Participants |
| Cohort 2 | Left Ventricular Opacification (LVO) | LVO grade of 3 (complete) | 12 Participants |
| Cohort 3 | Left Ventricular Opacification (LVO) | LVO grade of 2 (moderate) or 3 (complete) | 12 Participants |
| Cohort 3 | Left Ventricular Opacification (LVO) | LVO grade of 3 (complete) | 12 Participants |