A Phase 3, Multi-Center, Open Label Safety Study of RSD1235 in Subjects with Atrial Fibrillation. - ACT IV

• Conditions: Arrhythmias are abnormal rhythms of the heart. The term arrhythmia refers to a deviation from the normal sequence of initiation and conduction of electrical impulses, which cause the heart to beat. Arrhythmias may occur in the atria or the ventricles. Atrial arrhythmias are widespread and relatively benign.; MedDRA version: 61Level: PTClassification code 10003658

• Registration Number: EUCTR2005-004195-20-SE
• Lead Sponsor: Astellas Pharma US, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-20
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1.Subject or the subject’s legally authorized representative (parent or legal guardian) must comprehend and sign a written informed consent and at US sites, HIPAA Authorization; and at European sites, per EU Privacy Directive as implemented by member states in national law, as applicable;
2.Subject must be 18 years of age or older;
3.Subject who is female must be non-pregnant, non-nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 30-day follow-up. Methods of birth control considered to be effective would include hormonal contraception (the pill), an intrauterine device (IUD), condoms in combination with a spermicidal cream, total abstinence or sterilization;
4.Subject must have symptomatic AF that has been sustained for greater than 3 hours and less than or equal to 45 days. The presence of atrial arrhythmia will be documented by a 12-lead ECG recording at Screening. Atrial fibrillation is characterized by atrial activity which is either absent or chaotic both in amplitude and in rate;
5.Subject must have adequate anticoagulant therapy in the judgment of the Investigator. (If AF has lasted more than 48 hours then subjects should be managed in accordance with standard of practice as recommended by ACC/AHA/ESC practice guidelines) (Fuster V et al, 2001);
6.Subject must have systolic blood pressure (BP) above 90 mmHg and less than 160 mmHg and diastolic BP less than 95 mmHg at screening and baseline. (Note: Blood pressures will be measured 3 times within 5 minutes, after resting supine for 5 minutes and averaged to determine a baseline BP);
7.Subject must have a body weight between 45 and 136 kg (99 and 300 lbs).

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

1.Have known or suspected prolonged QT or uncorrected QT interval of >0.440sec as measured at Screening on a 12 lead ECG, familial long QT syndrome, or previous Torsades de Pointes;
2.Have symptomatic bradycardia or ventricular rate less than 50 bpm as documented by 12-lead ECG at Screening, unless controlled by a pacemaker;
3.Have a QRS interval > 0.14 sec unless subject has pacemaker at screening;
4.Have Class IV congestive heart failure (HF), HF requiring intravenous inotrope therapy, or be in cardiogenic or septic shock or other forms of shock requiring vasopressors or mechanical ventilation;
5.Have a Myocardial Infarction (MI), acute coronary syndrome, cardiac surgery (including PTCA or Stent placement), within 30 days prior to enrollment;
6.Have significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis;
7.Have failed electrical cardioversion;
8.Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to enrollment, or have previously received RSD1235;
9.Have any known secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, acute pericarditis or hypoxemia (oxygen saturation less than 90% on room air);
10.Have serious pulmonary, hepatic, metabolic, renal, gastrointestinal, central nervous system or psychiatric disease, infection, febrile illness (oral temperature > 38.5°C), end stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise subject safety;
11.Have uncorrected electrolyte imbalance (serum potassium of less than 3.5 mmol/L must be corrected and documented 6 hours or less prior to enrollment);
12.Have clinical evidence of digoxin toxicity in the opinion of the Investigator;
13.Have received intravenous Class I or Class III antiarrhythmic drugs or IV amiodarone within 24 hours prior to the start of the first study drug infusion;
14.Be unable to communicate well with the Investigator and to comply with the requirements of the entire study;
15.Have any other surgical or medical condition that, in the judgment of the Investigator might warrant exclusion or be contraindicated for safety reasons;
16.Have previously been randomized to an RSD1235 study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of RSD1235 in subjects with atrial fibrillation (AF).;Secondary Objective: To evaluate the efficacy measured by the rate of conversion of atrial fibrillation to sinus rhythm for a minimum of 1 minute within 1,5 hours from the start of the first infusion (Time=0).;Primary end point(s):