Atrial Fibrillation
Conditions
Brief summary
Explorative study in Atrial Fibrillation patients to assess Safety and Pharmacokinetics at initiation of treatment and at steady state
Interventions
DRUGAZD1305
AZD1305 loading dose 250 mg + 125 mg evening dose on Study Day 1, maintenance dose 125 mg twice daily from Study Day 2
DRUGPlacebo
Placebo corresponding to AZD1305 loading dose + evening dose on Study Day 1, maintenance dose twice daily from Study Day 2
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum QTcF | During treatment days 2-10 | Maximum of all QTcF values obtained for any given patient from randomisation until the intended end of the study drug period, day 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) | During treatment days 2-10 | Number of patients who had at least one AE according to the definition in the study protocol |
| Estimated Cmax (Maximum Plasma Concentration) (PK Modeling) at Steady-state | During treatment days 1-10 | Population PK model parameter estimates derived from plasma concentrations of AZD1305 |
| Compliance With Trans Telephonic Monitoring (TTM) | During treatment days 1-10 | Percentage of twice daily TTM recordings (individual compliance) transmitted and available for analysis |
Countries
Denmark, Norway, Poland, Russia, Slovakia, Sweden
Participant flow
Pre-assignment details
All patients will attend a pre-entry Visit 3-28 days before the planned randomisation. At this Visit, the Investigator ensures that a signed Informed Consent Form has been obtained before any study specific procedures are conducted. Patients who have given their consent to participate in the study will then undergo a full clinical assessment
Participants by arm
| Arm | Count |
|---|---|
| AZD1305 Group A AZD1305 group A loading dose 250 mg + 125 mg evening dose on Study Day 1, maintenance dose 125 mg twice daily from Study Day 2 | 21 |
| AZD1305 Group B AZD1305 loading dose 500 mg + placebo evening dose on Study Day 1, maintenance dose 125 mg twice daily from Study Day 2 | 22 |
| Placebo Placebo corresponding to AZD1305 loading dose + evening dose on Study Day 1, maintenance dose twice daily from Study Day 2 | 22 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 2 |
| Overall Study | Lack of Efficacy | 2 | 0 | 4 |
| Overall Study | QTcF>550 ms | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | AZD1305 Group A | AZD1305 Group B | Placebo | Total |
|---|---|---|---|---|
| Age Continuous Age (years) | 65 Years STANDARD_DEVIATION 10 | 64 Years STANDARD_DEVIATION 10 | 64 Years STANDARD_DEVIATION 9 | 64.5 Years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 14 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / — | 12 / — | 9 / — |
| serious Total, serious adverse events | 0 / — | 3 / — | 0 / — |
Outcome results
Primary
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.
Time frame: During treatment days 2-10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1305 Group A and AZD1305 Group B | Maximum QTcF | 461 ms | Full Range 417 |
| Placebo | Maximum QTcF | 427 ms | Full Range 383 |
Secondary
Adverse Events (AE)
Number of patients who had at least one AE according to the definition in the study protocol
Time frame: During treatment days 2-10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD1305 Group A and AZD1305 Group B | Adverse Events (AE) | 22 Participants |
| Placebo | Adverse Events (AE) | 13 Participants |
Secondary
Compliance With Trans Telephonic Monitoring (TTM)
Percentage of twice daily TTM recordings (individual compliance) transmitted and available for analysis
Time frame: During treatment days 1-10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1305 Group A and AZD1305 Group B | Compliance With Trans Telephonic Monitoring (TTM) | 97.4 Percentage of recordings analysed | Full Range 80 |
| Placebo | Compliance With Trans Telephonic Monitoring (TTM) | 96.4 Percentage of recordings analysed | Full Range 68.2 |
| Placebo | Compliance With Trans Telephonic Monitoring (TTM) | 98.3 Percentage of recordings analysed | Full Range 72.7 |
Secondary
Estimated Cmax (Maximum Plasma Concentration) (PK Modeling) at Steady-state
Population PK model parameter estimates derived from plasma concentrations of AZD1305
Time frame: During treatment days 1-10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1305 Group A and AZD1305 Group B | Estimated Cmax (Maximum Plasma Concentration) (PK Modeling) at Steady-state | 0.41 μmol/L | Full Range 0.17 |
| Placebo | Estimated Cmax (Maximum Plasma Concentration) (PK Modeling) at Steady-state | 0.45 μmol/L | Full Range 0.24 |