E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
AI-700 is an intravenous (IV) ultrasound contrast agent designed for echocardiographic imaging for myocardial defect detection. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061024 |
E.1.2 | Term | Cardiac disorder |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objectives of the study are:
1) to evaluate and optimize settings for AI-700-enhanced echocardiographic imaging on several ultrasound imaging platforms;
2) to evaluate the performance of AI-700 for echocardiographic imaging on several ultrasound imaging platforms; and
3) to collect additional safety data for AI-700 in healthy volunteers and stable cardiac patients. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Up to 60 men and non-pregnant/non-lactating women who are 18 to 70 years of age and who have undergone echocardiographic imaging within 14 days before AI-700 administration will be enrolled. The study will include both healthy volunteers and stable cardiac patient candidates.
Inclusion Criteria – Healthy Volunteers
• Male or female between 18 and 70 years of age; • In good health, as determined by medical history, physical examination, vital signs, and 12-lead ECG; • If female, must be at least 1 year post-menopausal or surgically sterile; or be sexually abstinent or have a sterile sexual partner; or from 4 weeks before dosing until 30 days post-dosing use oral, implantable, or injectable contraceptives or an approved form of contraception (including intrauterine device [IUD], female condom, diaphragm with spermicidal, cervical cap, or use of a condom by sexual partner); • If female, have a negative serum pregnancy test within 24 hours of AI-700 if pre-menopausal or <1 year post menopausal; • Willingness to provide the Sponsor with access to data associated with his/her Qualification Echo performed during the 14 days prior to AI-700 dosing; • Able to comprehend and willing to sign an informed consent form; • Must have a low chance of coronary artery disease (CAD) as defined by medical history, ECG, the Qualification Echo, CAD risk factors, and (if available) a negative nuclear imaging study and/or a negative ECG stress test.
Inclusion Criteria – Stable Cardiac Patients
• Male or female and 18 to 70 years of age; • In stable health, as determined by medical history, physical examination, vital signs, and 12 lead ECG; • History of myocardial infarction (MI) and/or coronary artery revascularization procedure at least 90 days prior to AI-700 dosing; • Willingness to provide the Sponsor with access to data associated with his/her Qualification Echo performed during the 14 days prior to AI-700 dosing; • If female, must be at least 1 year post-menopausal or surgically sterile; or be sexually abstinent or have a sterile sexual partner; or from 4 weeks before dosing until 30 days post-dosing use oral, implantable, or injectable contraceptives or an approved form of contraception (including intrauterine device (IUD), female condom, diaphragm with spermicidal, cervical cap, or use of a condom by sexual partner); • If female, have a negative serum pregnancy test within 24 hours of AI-700 if pre-menopausal or <1 year post-menopausal; • Able to comprehend and willing to sign an informed consent form.
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E.4 | Principal exclusion criteria |
Exclusion Criteria - Healthy Volunteers
• Significant intra-cardiac shunt or any other cardiovascular structural and/or severe functional abnormality on the Qualification Echo, unless deemed not clinical relevant by the Investigator and approved by the Sponsor in writing; • Ejection fraction (EF, estimated from Qualification Echo) ≤55% (outside normal range); • Oxygen saturation <92% at rest; • Females who are pregnant or lactating; • A history or clinical manifestations of significant mental illness or significant pulmonary, hematological, renal, hepatic, central nervous, cardiovascular, genitourinary, or gastrointestinal disorders, or diabetes; • A history of any major surgical procedure within 90 days of Screening/Baseline; • Body mass index (BMI) >35; • Inadequate visualization of 3 or more segments in the 4-chamber apical view for evaluation of cardiac function during the Qualification Echo; • Sitting systolic blood pressure <90 mmHg or >150 mmHg, diastolic blood pressure <50 mmHg or >95 mmHg, pulse rate <45 bpm or >90 bpm; • Frequent PVCs or PACs (defined as >5 PVCs and/or PACs per minute); • Any ≥2nd AV block, bundle branch block (BBB), or rhythm abnormality; • History of non-seasonal asthma within the past 3 years or a recent history of seasonal asthma requiring prescription medications to control; • Participated in a clinical study involving an investigational drug or device within 30 days prior to AI-700 administration (90 days for subjects in the UK); • Previous participation in an AI-700 clinical trial
Exclusion Criteria – Stable Cardiac Patients
• Any clinically unstable condition documented within 30 days prior to AI-700 administration or at Screening/Baseline. These conditions include, but are not limited to: severe arterial hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >120 mmHg) or pulmonary hypertension (>60 mmHg systolic), or any increase in pulmonary pressures felt to be due to increased pulmonary vascular resistance; hypotension (sitting systolic blood pressure <90 mmHg, diastolic blood pressure <50 mmHg); bradycardia or tachycardia (pulse rate <45 bpm or >100 bpm); history of any major surgical procedure; or exacerbation of chronic obstructive pulmonary disease (COPD) of any severity, irrespective of hospitalization. • Recent history (past 6 months) of typical or atypical chest pain (angina), or unstable angina; • Congestive heart failure (CHF) graded as New York Heart Association Class 3 or 4 within 90 days of dosing; • COPD, with FEV1<50% of predicted, FEV1/FVC<75% of predicted, measured within 6 months prior to dosing; • Significant left main coronary artery disease (≥50% stenosis), if known; • Any revascularization procedure within 90 days prior to AI-700 administration; • Female who is pregnant or lactating; • Cerebrovascular accident or transient ischemic attack within 90 days prior to AI-700 administration; • Significant cardiovascular structural abnormality, including intra-cardiac shunts; uncorrected congenital heart disease (i.e., patent foramen ovale); idiopathic, severe valvular disease; large amount of pericardial effusion; as determined by the Qualification Echo, unless deemed not clinically significant by the Investigator and approved by the Sponsor; • EF (estimated from Qualification Echo) <40 %; • Inadequate visualization of 3 or more segments in the 4-chamber apical view for evaluation of cardiac function during the Qualification Echo; • Oxygen saturation <90% at rest; • Uncontrolled atrial fibrillation or frequent premature ventricular contractions (PVCs) or premature atrial contractions (PACs) (defined as >5 PVCs and/or PACs per minute); • History of QT/QTc prolongation (QT/QTc >500 msec); • New or changing ECG abnormalities at any time between Screening and AI-700 dosing; • Any ≥2nd AV block, BBB, or rhythm abnormality that has not been evaluated and treated by a specialist or for which current treatment is not adequately effective to the extent that subject safety is assured; • Use of automatic implantable cardioverter/defibrillator; • History of non-seasonal asthma within the past 3 years or a recent history of seasonal asthma requiring prescription medications to control; • Organ transplant or end-stage failure of a major organ; • Active seizure disorder and/or any episode of seizure in the past 6 months; • Participated in a clinical study involving an investigational drug or device within 30 days prior to AI 700 administration (90 days for subjects in the UK); • Significant pulmonary structural or functional abnormality (e.g. lobectomy of the lung); • Previous participation in an AI-700 clinical trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main objective of this study is to explore AI-700 imaging techniques on several platforms not yet tested. No statistical efficacy analyses will be performed. The performance of AI-700 Echo contrast with regards to myocardial contrast enhancement will be evaluated using different ultrasound platforms. The analyses will be based on review of the imaging data by the Sponsor/designee. Any patient who receives AI-700 will have images reviewed, irrespective of the quality and/or completeness of the data.
Safety will be assessed based on a review of adverse events, clinical laboratory evaluations (hematology, coagulation, and serum chemistry), vital signs monitoring (including pulse oximetry), ECGs, US-ECGs, injection site monitoring, review of concomitant medications, and physical examinations. When blood sample collections and other safety assessments (vital signs, 12-lead ECG, etc.) occur at the same timepoint, ECG and vital signs will be collected first at the scheduled timepoints, and other safety assessments will be performed after collection of the blood sample. Additional safety assessments will be acquired for any subject for whom it is deemed necessary (e.g., for an AE) by the Investigator. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will be completed at the follow-up visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |