INO-1001 is being developed for the treatment of high-risk subjects undergoing cardiopulmonary bypass (CPB) for coronary revascularization and/or valve surgery.
Conditions
Interventions
Product Name: INO-1001
Product Code: NA
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: 9-[N- (3-morpholinopropyl)-aminosulfonyl]-5,6-dihydro-5-oxo-11-H-indeno [1,2-c] isoqu
Sponsors
Inotek Pharmaceuticals Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: 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. ;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 | — |
Countries
Czech Republic
Outcome results
None listed