E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recent Onset Atrial Fibrillation or Flutter |
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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 demonstrate the superiority of tedisamil sesquifumarate to placebo in the rapid conversion to normal sinus rhythm (for at least 60 seconds), as measured by the percentage of subjects converted at any time within 2.5 hours after the start of infusion
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E.2.2 | Secondary objectives of the trial |
To determine the percentage of subjects:
converting to normal sinus rhythm (NSR) within 2.5 hours after start of the intravenous infusion and in NSR at 2.5 hours after initiation of the infusion of tedisamil vs placebo
converting to NSR within 2.5 hours after start of the intravenous infusion and in NSR at 24 hours after initiation of the infusion of tedisamil vs placebo
converting to NSR within 2.5 hours after start of the intravenous infusion and in NSR at hospital discharge after initiation of the infusion of tedisamil sesquifumarate vs placebo
To determine:
the time to conversion to NSR after the start of the infusion of tedisamil vs placebo
the energy required for DC cardioversion of tedisamil vs placebo
Piggy-back pharmacoeconomic evaluation of tedisamil on pooled subject population from designated tedisamil studies
The safety objective of this study is to determine the safety and tolerability of tedisamil vs placebo |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects may be included in the study only when they meet all of the following criteria:
1. Willing to sign informed consent before screening examinations are performed and before the study drug is administered
2. Female, > 18 years of age
3. Subjects with documented (60 seconds rhythm strip) symptomatic atrial fibrillation or flutter (duration > 3 hours and < 45 days) at the time of randomization
4. Subjects who are in no distress and hemodynamically stable (supine systolic blood pressure > 90 mmHg and diastolic blood pressure < 105 mmHg) |
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E.4 | Principal exclusion criteria |
Subjects will be excluded from the study for any of the following reasons:
1. Male gender
2. Any woman who is pregnant, lactating, or not using medically acceptable contraception.
3. Evidence of severe hematologic, immunologic, respiratory, urogenital, gastrointestinal, hepatic, renal, endocrinologic, metabolic, nutritional, psychiatric, dermatologic, connective tissue, musculoskeletal, malignant or other relevant disease, allergy or surgery, as revealed by history, physical examination and/or laboratory assessments which may limit participation in or prevent completion of the study
4. Clinical evidence of hyperthyroidism
5. Demonstrated atrial or ventricular thrombus or valvular vegetation during trans-esophageal echocardiogram
6. History of a cerebrovascular accident within six months prior to randomization
7. Congestive heart failure of NYHA functional Class IV
8. History of rheumatic heart disease
9. Acute coronary syndromes at the time of randomization
10. Known history and/or electrocardiographic evidence of ventricular pre-excitation
11. History of life-threatening ventricular arrhythmias including Torsade de Pointes
12. Previous electrocardiographic evidence of second or third degree AV block
13. Sick sinus syndrome
14. Ventricular rate < 50 bpm or > 200 bpm documented by 12-lead ECG
15. Myocardial infarction within 30 days prior to randomization
16. Cardiac surgery within 3 months prior to randomization
17. Need for external and internal pacemaker
18. Stent placement or PTCA within 30 days prior to randomization
19. Congenital long QT syndrome
20. QTc interval > 470 ms prior to randomization.
21. Serum creatinine > 1.8 mg/dl (159 µmol/l)
22. Serum potassium < 4.0 mEq/L (< 4.0 mmol/l)
23. Serum magnesium < 0.8 mmol/L
24. Suspicion or evidence of digitalis intoxication
25. Concurrent treatment with antiarrhythmic drugs (except for digitalis, diltiazem, or ß-blockers), not discontinued for at least five half-lives before randomization. Sotalol is disallowed medication.
26. Treatment with amiodarone within three months prior to randomization
27. Participation in a previous tedisamil clinical study
28. Participation in a clinical trial and/or intake of an investigational drug within four weeks prior to the screening visit.
29. Any history of drug abuse, including alcohol, within one year of screening visit
30. Serious drug allergy or any history of serious abnormal drug reaction
31. Severe valvular heart disease
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E.5 End points |
E.5.1 | Primary end point(s) |
the percentage of subjects converted to normal sinus rhythm (NSR) at any time within 2.5 hours of the infusion start. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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
| Information not present in EudraCT |
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 |
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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
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |