E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
INO-1001 is being developed for the treatment of high-risk subjects undergoing cardiopulmonary bypass (CPB) for coronary revascularization and/or valve surgery. |
|
MedDRA Classification |
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 |
To demonstrate that intravenous INO-1001 is safe and tolerable when administered to subjects undergoing elective CPB for coronary revascularization and/or valve surgery.
To demonstrate that INO-1001 reduces a composite endpoint of major post-operative complications during the first 30 post-operative days in high-risk subjects undergoing elective CPB for coronary revascularization and/or valve surgery. |
|
E.2.2 | Secondary objectives of the trial |
To demonstrate that INO-1001 improves post-operative clinical outcomes and physiologic parameters during the first 30 post-operative days in high risk subjects undergoing elective CPB for coronary revascularization and/or valve surgery.
Assessment of the pharmacokinetic profile of intravenous INO-1001 administered to subjects undergoing elective CPB for coronary revascularization and/or valve surgery.
Assessment of the effect of intravenous INO-1001 on cardiac biomarkers in subjects undergoing elective CPB for coronary revascularization and/or valve surgery.
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
All eligible subjects must meet all of the following criteria: • Scheduled to undergo elective cardiopulmonary bypass for coronary revascularization and/or valve surgery • Written informed consent must be obtained prior to participation • Age eighteen (18) to ninety (90) years (inclusive) • Males and non-pregnant non-lactating femals of child-bearing potential who agree to use two effective methods of contraception (e.g. condom and spermicide) for three (3) months following exposure to the study drug. • Third (Main) Phase ONLY: European System for Cardiac Operative Risk Evaluation (euroSCORE) equal to or greater than six calculated at any time within ninety-six hours prior to anticipated study drug administration. |
|
E.4 | Principal exclusion criteria |
To be eligible for entry into the study, subjects must not have any of the following criteria: • History of a hypersensitivity reaction to more than three drugs or to mannitol • Participation in any other investigational study within thirty (30) days of the Screening Phase • Myocardial infarction within seventy-two (72) hours of the study drug infusion • Clinically significant abnormalities in any clinical laboratory tests, as judged by a Clinical Investigator • Clinically significant hematological, hepatic, renal, pulmonary, or gastrointestinal disorder, as judged by a Clinical Investigator • Any known malignancy other than treated basal cell skin cancer or cervical carcinoma in situ • Dialysis, creatinine > 2 mg/dl, or ALT or AST above the upper limits of normal • History of Hepatitis B, Hepatitis C, acute or chronic hepatitis, or history / demonstration of HIV antibodies or AIDS • Female subjects who are currently pregnant, lactating, or have a positive pregnancy test • Any recent (acute) or chronic medical, psychological or social issue that in the opinion of the investigator might interfere with the performance, completion, or interpretation of this study • Subjects who have received an irreversible CYP3A4 inhibitor orally or parenterally within approximately three (3) days of study drug administration, including azole antifungals (e.g. ketoconazole, itraconazole, miconazole, fluconazole); macrolide antibiotics (e.g. clarithromycin, erythromycin, troleandomycin; but not azithromycin); HIV-related protease inhibitors (e.g. Crixivan [Indinavir], Invirase [saquinavir], Norvir [ritonavir], and Viracept [nelfinavir]); the anti-depressant nefazodone; and the long-acting benzodiazepines (e.g. diazepam). • Subjects who have received the potent irreversible CYP3A4 inhibitors verapamil or diltiazem within approximately seven (7) days of study drug administration. • Subjects who have received amiodarone within thirty (30) days of the study drug administration • Subjects with repeated demonstration of a QTc intervals > 450 msecs or known Long QT Syndrome • Known alcohol or drug abuse within the last year
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be a reduction in a composite endpoint consisting of any one of the following major post-operative complications which occur during the Treatment, Observation, or Followed-Up Phases: • thirty day all-cause mortality • prolonged mechanical ventilation, as defined by mechanical ventilatory support > seventy-two hours following arrival in the intensive care unit / recovery room • renal dysfunction, as defined by a need for renal replacement therapy (dialysis or CVVH) • profound cardiac failure, as defined by requirement of a left ventricular assist device or prolonged use of intravenous vasopressors or inotropic agents, as defined by usage more than forty-eight (48) hours following arrival in the intensive care unit / recovery room |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
|
The Follow-Up Phase on Day 30, is considered as the end of trial. A subject may withdrawn from the study under the following conditions: a. Subject withdraws consent b. Subject compliance to the protocol is poor c. Any condition that in the physician's opinion may cause risk to the subject. In this case, the Investigator should specify on the CRF the reason for subject's withdrawal. In all cases of early subject withdrawal all study termination procedures should be followed.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 12 |