Left Ventricle Function
Conditions
Keywords
AZD1305, anti-arrhythmics, safety
Brief summary
To explore if AZD1305 compromises left ventricular performance in patients with left ventricular dysfunction
Interventions
DRUGAZD1305
iv single infusion: initial iv loading dose which will be followed by a maintenance dose given for a maximum of 90 minutes
DRUGPlacebo
iv single infusion: initial iv loading dose which will be followed by a maintenance dose given for a maximum of 90 minutes
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male patients and postmenopausal women * Mildly/moderately decreased heart function * Regular heart rhythm
Exclusion criteria
* Potassium outside normal reference values * Child bearing potential * Severely decreased heart function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF), Change From Baseline | From the iv loading dose during 30 min and the following maintenance iv dose during a maximum of 90 min. The infusion was stopped when all echocardiographic measurements had been carried out | To explore if AZD1305 compromises left ventricular performance in patients with left ventricular dysfunction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Reported Adverse Event During Each Study Period and in Each Dose Group | From randomisation to last study visit (mean infusion time 1.6 hours) | To evaluate the tolerability and safety of AZD1305 given as an iv infusion to patients with left ventricular dysfunction. |
| Area Under Curve (AUC) ( µmol*h/L) of AZD1305 | From the iv loading dose during 30 min and the following maintenance iv dose during a maximum of 90 min. | To evaluate the pharmacokinetics of AZD1305, given as an iv infusion, in patients with left ventricular dysfunction |
| QTcF Interval | Up to 24 hours following start of IV dosing. | Maximum QTcF observed for each patient. QTcF is the QT interval corrected for the RR interval using the Fridericia formula |
Countries
Sweden
Participant flow
Recruitment details
The study enrolled 33 patients and randomised 16 patients between August 2008 and July 2009 at a Clinical Pharmacology Unit located at a University Hospital in Sweden.
Pre-assignment details
Screening for eligibility and no significant changes in the medication for heart failure during the preceding 1 month before enrolment. In addition, patients for whom it was not possible to obtain high quality echocardiographic pictures were excluded from the study. The pre-entry visit was 30 days or less before the first dosing visit.
Participants by arm
| Arm | Count |
|---|---|
| AZD1305 Dose 1 and Dose 2 AZD1305 was given as an initial intravenous (iv) loading dose during 30 min followed by a maintenance iv dose during a maximum of 90 min. The infusion was stopped when all echocardiographic measurements had been carried out. The mean total dose of AZD1305 was 30 mg (range 29-31 mg) | 12 |
| Placebo Dose 1 and Dose 2 Sodium chloride was given as an initial iv loading dose during 30 min followed by a maintenance iv dose during a maximum of 90 min. The infusion was stopped when all echocardiographic measurements had been carried out | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | AZD1305 Dose 1 and Dose 2 | Placebo Dose 1 and Dose 2 | Total |
|---|---|---|---|
| Age Continuous | 5 Years STANDARD_DEVIATION 62 | 3 Years STANDARD_DEVIATION 65 | 4 Years STANDARD_DEVIATION 254 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 12 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 1 / 4 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Left Ventricular Ejection Fraction (LVEF), Change From Baseline
To explore if AZD1305 compromises left ventricular performance in patients with left ventricular dysfunction.
Time frame: From the iv loading dose during 30 min and the following maintenance iv dose during a maximum of 90 min. The infusion was stopped when all echocardiographic measurements had been carried out
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1305 Dose 1 and Dose 2 | Left Ventricular Ejection Fraction (LVEF), Change From Baseline | 2.00 Percent change | 95% Confidence Interval -0.6 |
| Placebo Dose 1 and Dose 2 | Left Ventricular Ejection Fraction (LVEF), Change From Baseline | -3.25 Percent change | 95% Confidence Interval -6.53 |
Secondary
Area Under Curve (AUC) ( µmol*h/L) of AZD1305
To evaluate the pharmacokinetics of AZD1305, given as an iv infusion, in patients with left ventricular dysfunction
Time frame: From the iv loading dose during 30 min and the following maintenance iv dose during a maximum of 90 min.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AZD1305 Dose 1 and Dose 2 | Area Under Curve (AUC) ( µmol*h/L) of AZD1305 | 2.04 µmol*h/L |
Secondary
Number of Subjects With at Least One Reported Adverse Event During Each Study Period and in Each Dose Group
To evaluate the tolerability and safety of AZD1305 given as an iv infusion to patients with left ventricular dysfunction.
Time frame: From randomisation to last study visit (mean infusion time 1.6 hours)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD1305 Dose 1 and Dose 2 | Number of Subjects With at Least One Reported Adverse Event During Each Study Period and in Each Dose Group | 0 Participants |
| Placebo Dose 1 and Dose 2 | Number of Subjects With at Least One Reported Adverse Event During Each Study Period and in Each Dose Group | 0 Participants |
Secondary
QTcF Interval
Maximum QTcF observed for each patient. QTcF is the QT interval corrected for the RR interval using the Fridericia formula
Time frame: Up to 24 hours following start of IV dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD1305 Dose 1 and Dose 2 | QTcF Interval | 446 ms | 95% Confidence Interval 409 |
| Placebo Dose 1 and Dose 2 | QTcF Interval | 445 ms | 95% Confidence Interval 437 |