Paroxysmal atrial fibrillation MedDRA version: 16.1 Level: LLT Classification code 10034039 Term: Paroxysmal atrial fibrillation System Organ Class: 100000004849
Conditions
Interventions
Product Name: XEN-D0103
Product Code: XEN-D0103
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: None
CAS Number: None
Current Sponsor code: XEN-D0103
Other descriptive name: XEN-D0103
Concentr
Sponsors
Xention Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. Patients of either sex, aged 18 years and older with paroxysmal AF confirmed within 6 months prior to Screening and Washout. 3. Dual chamber pacemaker with appropriate arrhythmia diagnostics for at least 1 month prior to Screening and Washout 4. Able to tolerate withdrawal of Class I and III antiarrhythmic drugs (such as Flecainide, Sotalol, Dronedarone or Amiodarone). 5. Able to tolerate pacemaker antiarrhythmic algorithms being turned off at Screening and Washout, if applicable. 6. Evidence of AF burden 1% and 50% prior to Visit 2 (Day 1). 7. Anticoagulated in accordance with European Society of Cardiology (ESC) Guidelines. 8. Women must be of non child bearing potential. Non-child bearing potential is defined as amenorrheic for at least 2 years AND have serum follicle stimulating hormone [FSH] level of at least 30 IU/L) or have undergone a hysterectomy or bilateral oophorectomy (tubal ligation is not acceptable). If partners of male patients are of childbearing potential, the patient must be willing to use contraception (e.g. condoms).In addition, their female partner must also be using contraception (e.g. hormonal, intra-uterine device etc). This double contraception must be used from the first dose of study drug until at least 90 days after the last dose of study drug 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Cardiac ablation procedure within 3 months prior to Screening and Washout. 2. QTc interval >450 ms on Day 1. 3. History of clinically significant ventricular arrhythmia. 4. History of long QT syndrome. 5. Concomitant treatment with any Class I or III anti-arrhythmic drugs (such as Flecainide, Sotalol, Dronedarone or Amiodarone) on Day 1. Treatment with oral Amiodarone must be stopped 6 weeks prior to Study Day 1. In the case of intravenous Amiodarone, a cumulative dose of >5g in the period between Screening and Washout and Day 1 is unacceptable. In the case of all other Class I or III anti-arrhythmic drugs, they must be stopped for at least 2 weeks prior to Day 1. 6. Heart failure with symptoms consistent with New York Heart Association [NYHA] classes III-IV. Patients with NYHA I-II heart failure can be enrolled if there have beenno hospital admissions for exacerbations of heart failure within 6 months prior to screening 7. Myocardial infarction within 3 months of Screening and Washout; coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) within 6 months of Screening and Washout, or unstable angina within 3 months of the Screening and Washout. 8. Transient ischaemic attack (TIA) or stroke within 3 months of Screening and Washout. 9. Body mass index (BMI) >36 kg/m2 at Screening and Washout. 10. Patient is unable or unwilling to co-operate with the study procedures. 11. Participation in any other clinical trials within 30 days prior to Screening and Washout. 12. Substance or alcohol abuse (as defined by Diagnostic and Statistical Manual of Mental Disorders Forth Edition) within 6 months of Screening and Washout. 13. The following laboratory abnormalities at Screening and Washout, with the provision that repeat samples may be considered for this criterion at the discretion of the Sponsor: a. Serum potassium of 5.5mmol/L b. Serum magnesium 1.5x ULN. f. Serum haemaglobin <9g/L (women) or 11g/L (men) 14. Taking medication which is a CYP3A4 substrate with a narrow therapeutic window (see section 9.8.3) 15. Evidence of any other clinically significant disease or condition which in the opinion of the Investigator would preclude the patient's participation in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the reduction in AF burden (time spent in AF as a proportion of the analysis period) by XEN-D0103 (50 mg BID) compared to placebo in patients with paroxysmal AF.;Secondary Objective: • To assess the safety and tolerability of 28 days dosing with XEN D0103 (50 mg BID) in patients with paroxysmal AF. • To assess mean duration of AF episodes following XEN D0103 (50 mg BID) compared to placebo. • To assess the frequency of AF episodes following XEN D0103 (50 mg BID) compared to placebo. • To assess trough XEN D0103 concentrations. ;Primary end point(s): The primary endpoint will be AF burden, which is defined as the time spent in AF as a proportion of the analysis period.;Timepoint(s) of evaluation of this end point: Time spent in AF as a proportion of the analysis period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include: • the mean duration of AF episodes, • the frequency of AF episodes over the analysis period, • XEN D0103 plasma concentrations • the safety and tolerability of XEN-D0103 ;Timepoint(s) of evaluation of this end point: 28 days | — |
Countries
United Kingdom
Contacts
Public ContactChief Medical Officer
Xention Limited
Outcome results
None listed