E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with coronary artery disease or left ventricular dysfunction experiencing an acute coronary syndrome with non-life-threatening ventricular arrhythmias. |
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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 test the hypothesis that administration of GAP-486 is effective in decreasing the number of non-life-threatening ventricular arrhythmias in subjects who have acute coronary syndrome (unstable angina, ST segment elevated myocardial infarction [STEMI] or myocardial infarction without ST elevation [NSTEMI] subjects). |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability in subjects with acute coronary syndrome.To assess the dose-range and identify potentially effective doses for phase 3 studies. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men and surgically sterile or postmenopausal women 18 through 95 years of age. Postmenauposal women: at least 12 months of spontaneous amenorrhea or at least 6 months of spontaneous amenorrhea with serum FSH level > 40mIU/mL or at least 6 weeks postsurgical bilateral oophrectomy (with or without hysterectomy). - Subjects must fulfill clinical criteria for an acute ischemic event. - Subjects must have experienced at least 1 episode of non-sustained ventricular tachycardia (NSVT) or a self-terminating episode of sustained ventricular tachycardia before the 3-hour baseline Holter monitor is started. - Subjects will have test article within 36 hours from the episode of ischemia. |
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E.4 | Principal exclusion criteria |
-Subjects for whom percutaneous coronary intervention (PCI), thrombolytics, or CABG is anticipated during the 24-hour on-therapy phase of the study. However, revascularization procedures must not be delayed or withheld for the purposes of qualifying for or participating in the study. -Subjects who have had previous PCI, treatment with thrombolytics, CABG, or other cardiac surgeries within 24 hours prior to screening. -Subjects for whom (at the time of enrollment) cardiac angiography or stress testing is planned during the 24-hour on-therapy phase of the study. -Any antiarrhythmics (with the exception of beta blockers) given within 5 half-lives of the start of the 24-hour on-therapy phase of the study. -Subjects with cardiogenic shock -Subjects with acute pulmonary edema who do not respond immediately to diuretic treatment. -Documented history of torsade de pointes. -Known congenital long QT syndrome. -QTc > 0.50 second at screening. -Bradycardia < 40 beats per minute for > 1 minute or sinus pauses > 3 seconds while awake which occur anytime during the 30 minutes prior to test article administration. -Subjects with New York Heart Association (NYHA) Class IV Congestive Heart Failure (CHF). -Presence of or immediate need for continuous ventricular demand pacemaker. -Known significant hepatic dysfunction unrelated to the acute ischemic event or renal dysfunction -Subjects with hypokalemia at the time of Holter monitor placement. -Subjects with new onset atrial fibrillation of < 1 month duration or subjects with unknown duration of atrial fibrillation are excluded. However, if a subject has a negative transesophageal echo or is known to have chronic atrial fibrillation > 1 month and has been receiving anticoagulants for > 1 month, and meets all the inclusion/exclusion criteria, they are eligible to participate in the study. -Subjects with Wolff-Parkinson-White syndrome -Current use of investigational device or use of investigational drug within 30 days before entry into the study. -Subject who previously received test article in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Total number of ventricular arrhythmia beats (the sum of ventricular arrhythmia beats from premature ventricular contractions, couplets, and individual beats in each NSVT and sustained VT episode [see section 6.0 of the Protocol for definitions]) recorded by Holter monitoring during the 24-hour on-therapy phase. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Third-party unblinded and dose ranging |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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Enrollment rate achieved or if interim analysis provides results raising safety concerns |
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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 | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |