Explorative Study of AZD1305 in Atrial Fibrillation Patients

Study Overview
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Brief Summary
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Explorative study in Atrial Fibrillation patients to assess Safety and Pharmacokinetics at initiation of treatment and at steady state

Official Title
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A Randomised, Placebo-controlled, Double-blind, Parallel-group, Multicentre, Phase IIa Study to Explore the Relationship Between QTcF Interval at First Dose (Loading Dose) and at Steady State After Treatment With AZD1305 Extended-release Tablets or Placebo When Given to Patients With Documented AF

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: AZD1305
* Drug: AZD1305
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented Atrial Fibrillation but in stable SR for at least 2 h and a maximum of 28 days. Sinus rhythm at randomisation Exclusion Criteria: Haemodynamically unstable condition as judged by the Investigator, systolic BP <100 mmHg or >180 mmHg, or diastolic BP >105 mmHg at randomisation Personal or family history of Torsades de Pointes (TdP), any other polymorphic ventricular tachycardia (PVT), sustained ventricular tachycardia, long QT syndrome and/or Brugada syndrome Sinus bradycardia (<50 beats per minute (bpm)) at randomisation QTc (Fridericia, QTcF ) >450 ms measured in sinus rhythm at randomisation, Serum potassium below 3.8 or above 5.0 mmol/L or plasma potassium below 3.6 or above 5.0 mmol/L QRS duration >120 ms at randomisation Use of any antiarrhythmic drug class I and/or III, digitalis glycoside, QT prolonging drug and/or drug that inhibits CYP3A4, as well as St John's Worth

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1305 loading dose 250 mg + 125 mg<br>Tablets | Drug: AZD1305<br>* AZD1305 loading dose 250 mg + 125 mg evening dose on Study Day 1, maintenance dose 125 mg twice daily from Study Day 2<br>|
| Experimental: AZD1305 loading dose 500 mg + placebo<br>Tablets | Drug: AZD1305<br>* AZD1305 loading dose 500 mg + placebo evening dose on Study Day 1, maintenance dose 125 mg twice daily from Study Day 2<br>|
| Placebo Comparator: Placebo corresponding to AZD1305 loading dose<br>Tablets | Drug: Placebo<br>* Placebo corresponding to AZD1305 loading dose + evening dose on Study Day 1, maintenance dose twice daily from Study Day 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum QTcF | Maximum of all QTcF values obtained for any given patient from randomisation until the intended end of the study drug period, day 10. | During treatment days 2-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) | Number of patients who had at least one AE according to the definition in the study protocol | During treatment days 2-10 | 
| Estimated Cmax (Maximum Plasma Concentration) (PK Modeling) at Steady-state | Population PK model parameter estimates derived from plasma concentrations of AZD1305 | During treatment days 1-10 | 
| Compliance With Trans Telephonic Monitoring (TTM) | Percentage of twice daily TTM recordings (individual compliance) transmitted and available for analysis | During treatment days 1-10 |