Explorative Study of AZD1305 in Atrial Fibrillation Patients

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

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

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: AZD1305; Drug: AZD1305; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Research Site
  • Esbjerg, Denmark
    • Research Site
  • Hvidovre, Denmark
    • Research Site
  • Kobenhavn, Denmark
    • Research Site
  • Silkeborg, Denmark
    • Research Site
  • Svendborg, Denmark
    • Research Site
• Norway
  • Oslo, Norway
    • Research Site
  • RUD, Norway
    • Research Site
  • Tynset, Norway
    • Research Site
• Poland
  • Bytom, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
• Russian Federation
  • Moscow, Russian Federation
    • Research Site
  • Saint-petersburg, Russian Federation
    • Research Site
• Slovakia
  • Kosice, Slovakia
    • Research Site
  • Nitra, Slovakia
    • Research Site
  • Nove Zamky, Slovakia
    • Research Site
  • Rimavska Sobota, Slovakia
    • Research Site
• Sweden
  • Goteborg, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Kenneth Egstrup, Svendborg Sygehus, Forsknings-og udviklingsafd.

Publications and helpful links

General Publications

• Egstrup K, Bergfeldt L, Duris T, Gullestad L, Kochmanski M, Kusnierz B, Nielsen T, Sawicki S, Aunes-Jansson M, Edvardsson N, Frison L, Johansson S, Berggren A. QT response after a test dose and during maintenance therapy with AZD1305 in patients with atrial fibrillation: a double-blind, randomized, placebo-controlled trial. Am J Cardiovasc Drugs. 2011 Jun 1;11(3):199-208. doi: 10.2165/11591750-000000000-00000.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: March 20, 2008
• First Submitted That Met QC Criteria: March 20, 2008
• First Posted (Estimate): March 26, 2008

Study Record Updates

• Last Update Posted (Estimate): January 26, 2012
• Last Update Submitted That Met QC Criteria: December 21, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: D3190C00019; 2007-007058-79