E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The trial is to investigate the efficacy of the new drug ATI-2042 to reduce the atrial tachyarrhythmia burden in patients with paroxysmal atrial fabrilation. ATI-2042 is designed to act like Amiodarone but with fewer side effects. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003661 |
E.1.2 | Term | Atrial fibrillation paroxysmal |
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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 |
- To study the efficacy of ATI-2042 in reducing atrial tachyarrhythmia (AT/AF) burden in patients with PAF, compared to placebo, for 12 weeks of treatment. - To study the safety and tolerability of ATI-2042 for up to 12 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
- To study the effect of ATI-2042 versus placebo on the number and duration of AT/AF episodes. - To study the effect of ATI-2042 versus placebo on symptoms associated with PAF using a structured questionnaire. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18 and above. 2. Proven paroxysmal atrial fibrillation (ECG, Holter monitor, or pacemaker diagnosis obtained by the clinical site or patient’s prior medical record documenting clear evidence of a diagnosis of PAF). 3. Pacemaker with appropriate AF diagnostic and recording capabilities implanted for at least 6 weeks. Additional pacemaker requirements include: a. Dual chamber with bipolar leads. b. Able to diagnose and log atrial tachyarrhythmia events. c. Able to have atrial tachyarrhythmia treatment algorithms turned off. d. Capable of storing at least 4 weeks AT/AF data between downloads. e. Able to record and store electrograms. 4. Atrial P waves of adequate amplitude to allow accurate sensing and assessment of AT/AF episodes and no obvious indication of frequent oversensing or undersensing. 5. Able to have pacemaker atrial antitachyarrhythmia treatment algorithms turned off for the duration of the study. 6. Able to understand study requirements and willing to follow instructions, attend all required study visits, and undergo all planned tests. 7. Able and willing to sign an Institutional Review Board/Research Ethics Board (IRB/REB)-approved informed consent form to participate in this study. 8. Women: Unable to bear children, that is, post-menopausal (absence of vaginal bleeding or spotting) for at least one year or surgically sterile. 9. Men: Starting at the time of study drug administration until completion of the 12-week treatment period, must be willing to use an approved method of contraception (which may include use of a condom with spermicide or use by partner of oral, implantable, or injectable contraceptives, IUD, diaphragm with spermicide) or will have a sterile sex partner. |
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E.4 | Principal exclusion criteria |
1. Known allergy or hypersensitivity to amiodarone or iodine. 2. Chronic treatment with amiodarone within 3 months prior to screening. 3. Termination of previous amiodarone treatment for severe toxicity. 4. Cardioversion within 1 month of screening. 5. Treatment with catheter ablation within 3 months prior to screening. 6. Known severe left ventricular dysfunction (EF less than 25%). 7. CHF with NYHA Class III or IV. 8. Unstable angina, myocardial infarction, PTCA, or CABG within 3 months of screening. 9. Prior history of sustained ventricular tachycardia or Torsades de Pointes. 10. reatment with rhythm control medication (Singh-Vaughan Williams Class I or Class III) within five half-lives time of entry into baseline period (rate control drugs are alloeable). 11. Currently taking clinically necessary anti-arrhythmic treatment taht cannot be stopped for participation in this study. 12. Any clinically significant comorbidity or out-of-range laboratory values at screening that in the opinion of the Investigator or Medical Monitor would put the patient at unacceptable risk or interfere with the conduct of the study (such as end-stage renal disease, severe pulmonary disease or terminal cancer). 13. Treatment with any other investigational drug or device within 30 days prior to screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: - AT/AF burden (total time spent in AT/AF as a percentage of total observation time) over the 12-week treatment period. Safety: - Adverse event type and incidence. - Change from baseline in ECGs, clinical laboratory assessments, vital signs, physical examinations, chest X-rays. - Eye examinations and pulmonary function tests. |
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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 | 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 | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |