Trial Outcomes & Findings for Cardiac Electrophysiological Study (NCT NCT00616629)
NCT ID: NCT00616629
Last Updated: 2011-09-22
Results Overview
Absolute change, after - before infusion
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
Measurements were obtained twice, from the invasive electrophysiological measurements made before and 20 min (or more) after the start of administration of the investigational product
Results posted on
2011-09-22
Participant Flow
A total of 68 patients were enrolled into the study. The study randomised 55 patients and 50 of those patients received study drug. All patients who received study drug completed the study.
At the pre-entry visit, which took place within 14 days before the planned catheter ablation (Study Day), patients underwent a full clinical assessment including a physical examination, ECG recording, Bood pressure(BP)/heart rate measurement, routine laboratory tests, and transthoracic echocardiography (TTE, if not done within the prior 6 months).
Participant milestones
| Measure |
AZD1305 Dose Group 1
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
Corresponding placebo
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
14
|
14
|
2
|
12
|
|
Overall Study
COMPLETED
|
11
|
12
|
13
|
2
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
AZD1305 Dose Group 1
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
Corresponding placebo
|
|---|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
2
|
1
|
0
|
0
|
|
Overall Study
AV-block
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Cardiac Electrophysiological Study
Baseline characteristics by cohort
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=12 Participants
Corresponding placebo
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age Continuous
Age (years)
|
60 Years
STANDARD_DEVIATION 14 • n=5 Participants
|
62 Years
STANDARD_DEVIATION 6 • n=7 Participants
|
60 Years
STANDARD_DEVIATION 8 • n=5 Participants
|
50 Years
STANDARD_DEVIATION 23 • n=4 Participants
|
62 Years
STANDARD_DEVIATION 6 • n=21 Participants
|
56 Years
STANDARD_DEVIATION 14.5 • n=10 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
44 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Measurements were obtained twice, from the invasive electrophysiological measurements made before and 20 min (or more) after the start of administration of the investigational productAbsolute change, after - before infusion
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=11 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=11 Participants
Corresponding placebo
|
|---|---|---|---|---|---|
|
LAERP (Left Atrial Effective Refractory Period (ie, the Longest S1-S2 Interval That Fails to Result in Atrial Depolarisation))
|
11 ms
Full Range -15 • Interval -15.0 to 40.0
|
43 ms
Full Range 0 • Interval 0.0 to 210.0
|
55 ms
Full Range -5 • Interval -5.0 to 85.0
|
50 ms
Full Range 40 • Interval 40.0 to 60.0
|
-10 ms
Full Range -90 • Interval -90.0 to 30.0
|
SECONDARY outcome
Timeframe: Measurements were obtained twice, from the invasive electrophysiological measurements made before and 20 min (or more) after the start of administration of the investigational productAbsolute change, after - before infusion
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=12 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=11 Participants
Corresponding placebo
|
|---|---|---|---|---|---|
|
RAERP (Right Atrial Effective Refractory Period)
|
19 ms
Full Range -5 • Interval -5.0 to 40.0
|
42 ms
Full Range 0 • Interval 0.0 to 75.0
|
84 ms
Full Range -30 • Interval -30.0 to 165.0
|
135 ms
Full Range 100 • Interval 100.0 to 170.0
|
-12 ms
Full Range -90 • Interval -90.0 to 40.0
|
SECONDARY outcome
Timeframe: Measurements were obtained twice, from the invasive electrophysiological measurements made before and 20 min (or more) after the start of administration of the investigational productAbsolute change, after - before infusion
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=11 Participants
Corresponding placebo
|
|---|---|---|---|---|---|
|
VERP (Ventricular Effective Refractory Period)) and Other Electrophysiological and Electrocardiographic Variables; RR, P Wave Duration, PR, QRS, QTend, QTcF, QTtop, QTend - QTtop)
|
11 ms
Full Range -25 • Interval -25.0 to 30.0
|
41 ms
Full Range 5 • Interval 5.0 to 145.0
|
59 ms
Full Range 25 • Interval 25.0 to 110.0
|
65 ms
Full Range 45 • Interval 45.0 to 85.0
|
3 ms
Full Range -25 • Interval -25.0 to 40.0
|
SECONDARY outcome
Timeframe: Measurements were obtained twice, from the invasive electrophysiological measurements made before and 20 min (or more) after the start of administration of the investigational product. ECG measurements, including QTcF, are available from several additionaAbsolute change, after - before infusion
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=12 Participants
Corresponding placebo
|
|---|---|---|---|---|---|
|
QTcF (Interval From the Beginning of the Q or R Wave to the End of the T Wave in the Surface ECG, Corrected for Changes in RR Interval Using Fridericia' Formula =QT/RR1/3 Interval in Seconds)
|
20 ms
Full Range -2 • Interval -2.0 to 42.0
|
65 ms
Full Range 13 • Interval 13.0 to 150.0
|
79 ms
Full Range 31 • Interval 31.0 to 128.0
|
65 ms
Full Range 59 • Interval 59.0 to 70.0
|
4 ms
Full Range -51 • Interval -51.0 to 47.0
|
SECONDARY outcome
Timeframe: During and after infusionA total of 13 scheduled PK samples for each patient during and after infusion
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
Corresponding placebo
|
|---|---|---|---|---|---|
|
Cmax Observed for AZD1305
|
0.178 umol/L
Full Range 0.104 • Interval 0.104 to 0.279
|
0.692 umol/L
Full Range 0.368 • Interval 0.368 to 1.82
|
1.46 umol/L
Full Range 0.931 • Interval 0.931 to 2.81
|
2.41 umol/L
Full Range 2.24 • Interval 2.24 to 2.58
|
—
|
SECONDARY outcome
Timeframe: Based on PK samples during and after infusionA total of 13 scheduled PK samples for each patient during and after infusion
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
Corresponding placebo
|
|---|---|---|---|---|---|
|
AUC Total of AZD1305 (Umol*h/L)
|
1.54 umol*h/L
Full Range 0.97 • Interval 0.97 to 2.21
|
4.97 umol*h/L
Full Range 2.70 • Interval 2.7 to 10.0
|
10.3 umol*h/L
Full Range 5.71 • Interval 5.71 to 18.9
|
17.3 umol*h/L
Full Range 16.5 • Interval 16.5 to 18.2
|
—
|
SECONDARY outcome
Timeframe: During active treatment periodNumber of patients
Outcome measures
| Measure |
AZD1305 Dose Group 1
n=11 Participants
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 Participants
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 Participants
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 Participants
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=12 Participants
Corresponding placebo
|
|---|---|---|---|---|---|
|
Number of Patients Who Had at Least One AE
|
2 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
Adverse Events
AZD1305 Dose Group 1
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
AZD1305 Dose Group 2
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
AZD1305 Dose Group 3
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
AZD1305 Dose Group 4
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AZD1305 Dose Group 1
n=11 participants at risk
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 participants at risk
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 participants at risk
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 participants at risk
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=12 participants at risk
Corresponding placebo
|
|---|---|---|---|---|---|
|
Vascular disorders
Bradycardia And Hypotension
|
0.00%
0/11
|
8.3%
1/12
|
7.7%
1/13
|
0.00%
0/2
|
8.3%
1/12
|
Other adverse events
| Measure |
AZD1305 Dose Group 1
n=11 participants at risk
Loading dose 15 min at 43.5 mg/h, Maintenance dose maximum 60 additional min at 19.6 mg/h
|
AZD1305 Dose Group 2
n=12 participants at risk
Loading dose 15 min at 130.4 mg/h, Maintenance dose maximum 60 additional min at 58.7 mg/h
|
AZD1305 Dose Group 3
n=13 participants at risk
Loading dose 15 min at 325.9 mg/h, Maintenance dose maximum 60 additional min at 146.6 mg/h
|
AZD1305 Dose Group 4
n=2 participants at risk
Loading dose 15 min at 488.8 mg/h, Maintenance dose maximum 60 additional min at 220.0 mg/h
|
Placebo
n=12 participants at risk
Corresponding placebo
|
|---|---|---|---|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
9.1%
1/11
|
0.00%
0/12
|
0.00%
0/13
|
0.00%
0/2
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Muscoskeletal Chest Pain
|
9.1%
1/11
|
0.00%
0/12
|
0.00%
0/13
|
0.00%
0/2
|
0.00%
0/12
|
|
Eye disorders
Vision Blurred
|
0.00%
0/11
|
8.3%
1/12
|
0.00%
0/13
|
0.00%
0/2
|
0.00%
0/12
|
|
Nervous system disorders
Syncope Vasovagal
|
0.00%
0/11
|
0.00%
0/12
|
7.7%
1/13
|
0.00%
0/2
|
0.00%
0/12
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/13
|
50.0%
1/2
|
0.00%
0/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60