Trial Outcomes & Findings for Study to Investigate the Pharmacodynamic Effect of a Single Dose of AZD2516 in Healthy Male Subjects (NCT NCT01154634)
NCT ID: NCT01154634
Last Updated: 2012-08-30
Results Overview
Total number of reflux episodes 0 to 3 hours post meal
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
0 to 3 hours post meal
Results posted on
2012-08-30
Participant Flow
In total 25 participants were enrolled into the study at 2 medical centres (14 and 11 participants), 20 of them were randomised to treatment (10 at each medical centre) and all these 20 participants completed the study.
After enrolment, participant's eligibility for assignment to treatment was based on inclusion and exclusion criteria.
Participant milestones
| Measure |
First 5 mg, Then Placebo, Then 16 mg, Then 40 mg
period 1: AZD2516 5 mg, period 2: washout, period 3: placebo, period 4: washout, period 5: AZD2516 16 mg, period 6: washout, period 7: AZD2516 40 mg.
|
First 40 mg, Then 16 mg, Then Placebo, Then 5 mg
period 1: AZD2516 40 mg, period 2: washout, period 3: AZD2516 16 mg, period 4: washout, period 5: placebo, period 6: washout, period 7: AZD2516 5 mg.
|
First 16 mg, Then 5 mg, Then 40 mg, Then Placebo
period 1: AZD2516 16 mg, period 2: washout, period 3: AZD2516 5 mg, period 4: washout, period 5: AZD2516 40 mg, period 6: washout, period 7: placebo.
|
First Placebo, Then 40 mg, Then 5 mg, Then 16 mg
period 1: placebo, period 2: washout, period 3: AZD2516 40 mg, period 4: washout, period 5: AZD2516 5 mg, period 6: washout, period 7: AZD2516 16 mg
|
|---|---|---|---|---|
|
Period 1 - First Intervention
STARTED
|
4
|
7
|
4
|
5
|
|
Period 1 - First Intervention
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 1 - First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 2 - Washout
STARTED
|
4
|
7
|
4
|
5
|
|
Period 2 - Washout
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 2 - Washout
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3- Second Intervention
STARTED
|
4
|
7
|
4
|
5
|
|
Period 3- Second Intervention
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 3- Second Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4 - Washout
STARTED
|
4
|
7
|
4
|
5
|
|
Period 4 - Washout
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 4 - Washout
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 5 - Third Intervention
STARTED
|
4
|
7
|
4
|
5
|
|
Period 5 - Third Intervention
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 5 - Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 6 - Washout
STARTED
|
4
|
7
|
4
|
5
|
|
Period 6 - Washout
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 6 - Washout
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 7 - Fourth Intervention
STARTED
|
4
|
7
|
4
|
5
|
|
Period 7 - Fourth Intervention
COMPLETED
|
4
|
7
|
4
|
5
|
|
Period 7 - Fourth Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Investigate the Pharmacodynamic Effect of a Single Dose of AZD2516 in Healthy Male Subjects
Baseline characteristics by cohort
| Measure |
AZD2516 5 mg
n=4 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=7 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=4 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
n=5 Participants
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
Age (years)
|
31 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
25 years
STANDARD_DEVIATION 4.5 • n=7 Participants
|
28.8 years
STANDARD_DEVIATION 5.9 • n=5 Participants
|
23 years
STANDARD_DEVIATION 4.2 • n=4 Participants
|
26.95 years
STANDARD_DEVIATION 6.3 • n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 0 to 3 hours post mealPopulation: Data from two subjects (one in arm AZD2516 5 mg, and one in arm Placebo) were excluded from efficacy analysis due to incorrect medication received.
Total number of reflux episodes 0 to 3 hours post meal
Outcome measures
| Measure |
AZD2516 5 mg
n=19 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
n=19 Participants
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Reflux Episodes 0 to 3 Hours Post Meal
|
15.1 Episodes
Interval 1.0 to 149.0
|
12.5 Episodes
Interval 0.0 to 50.0
|
11.0 Episodes
Interval 0.0 to 41.0
|
12.7 Episodes
Interval 0.0 to 40.0
|
SECONDARY outcome
Timeframe: 0 to 3 hours post mealPopulation: Data from two subjects were excluded from efficacy analysis due to incorrect medication received Data from five visits from two subject were excluded form analysis due to deviations caused by technical problems.
Number of TLESRs 0 to 3 hours post meal were calculated based upon the manometric analysis fpr the 3-hour post-meal period.
Outcome measures
| Measure |
AZD2516 5 mg
n=18 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=19 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=18 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
n=18 Participants
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal
|
16.9 relaxations
Interval 8.0 to 51.0
|
16.2 relaxations
Interval 9.0 to 26.0
|
10.4 relaxations
Interval 2.0 to 31.0
|
16.8 relaxations
Interval 9.0 to 33.0
|
SECONDARY outcome
Timeframe: 0 to 12 hours post dosePopulation: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
Area under the plasma concentration vs. time curve from time zero to 12-hours post dose calculated by loglinear trapezoidal method
Outcome measures
| Measure |
AZD2516 5 mg
n=19 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration Curve(AUC)
|
251.5 nmol*h/L
Interval 188.4 to 335.7
|
906.6 nmol*h/L
Interval 732.7 to 1122.0
|
2825 nmol*h/L
Interval 2185.0 to 3653.0
|
—
|
SECONDARY outcome
Timeframe: 1 to 4 hours post dosePopulation: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
Average plasma concentration
Outcome measures
| Measure |
AZD2516 5 mg
n=19 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Average Plasma Concentration (C Average)
|
45.46 nmol/L
Interval 35.04 to 58.98
|
175.8 nmol/L
Interval 142.4 to 217.1
|
506.8 nmol/L
Interval 405.0 to 634.3
|
—
|
SECONDARY outcome
Timeframe: 0 to 12 hours post dosePopulation: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
Maximum plasma concentration
Outcome measures
| Measure |
AZD2516 5 mg
n=19 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)
|
103.8 nmol/L
Interval 76.09 to 141.5
|
378.0 nmol/L
Interval 315.0 to 453.5
|
911.7 nmol/L
Interval 767.3 to 1083.0
|
—
|
SECONDARY outcome
Timeframe: 0 to 12 hours post dosePopulation: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
Time to maximum plasma concentration (Tmax)
Outcome measures
| Measure |
AZD2516 5 mg
n=19 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)
|
0.750 hours
Interval 0.5 to 4.0
|
0.750 hours
Interval 0.5 to 1.25
|
1.000 hours
Interval 0.5 to 4.0
|
—
|
SECONDARY outcome
Timeframe: 0 to 12 hours post dosePopulation: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received. Two samples were not analyzed for T half due to technical reasons.
Terminal half-life (T half)
Outcome measures
| Measure |
AZD2516 5 mg
n=17 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Terminal Half-life (T Half)
|
1.221 hours
Interval 1.042 to 1.43
|
1.416 hours
Interval 1.222 to 1.64
|
1.584 hours
Interval 1.414 to 1.774
|
—
|
SECONDARY outcome
Timeframe: Pre-entry to follow-upNumber of participants with clinically relevant change of laboratory variables as judged by the responsible medical officer.
Outcome measures
| Measure |
AZD2516 5 mg
n=20 Participants
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 Participants
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 Participants
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
n=20 Participants
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Clinically Relevant Change of Laboratory Variables
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
AZD2516 5 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
AZD2516 16 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
AZD2516 40 mg
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AZD2516 5 mg
n=20 participants at risk
Loading dose: 3 \* AZD2516 1 mg capsules. Maintenance doses: 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules and 1 \* AZD2516 1 mg capsule, 2 \* placebo capsules.
|
AZD2516 16 mg
n=20 participants at risk
Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule.
|
AZD2516 40 mg
n=20 participants at risk
Loading dose: 2 \* AZD2616 10 mg capsules, 1 \* placebo capsule. Maintenance dose: 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule and 2 \* AZD2616 5 mg capsules, 1 \* placebo capsule.
|
Placebo
n=20 participants at risk
Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules.
|
|---|---|---|---|---|
|
Nervous system disorders
Disturbance In Attention
|
10.0%
2/20
|
25.0%
5/20
|
20.0%
4/20
|
0.00%
0/20
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20
|
5.0%
1/20
|
35.0%
7/20
|
0.00%
0/20
|
|
Nervous system disorders
Headache
|
5.0%
1/20
|
15.0%
3/20
|
10.0%
2/20
|
0.00%
0/20
|
|
Nervous system disorders
Balance Disorder
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Nervous system disorders
Sinus Headache
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/20
|
|
Nervous system disorders
Somnolence
|
5.0%
1/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
10.0%
2/20
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Gastrointestinal disorders
Gastrointestinal Pain
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
|
Psychiatric disorders
Euphoric Mood
|
0.00%
0/20
|
10.0%
2/20
|
10.0%
2/20
|
0.00%
0/20
|
|
Psychiatric disorders
Daydreaming
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Eye disorders
Diplopia
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Eye disorders
Vision Blurred
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/20
|
|
Renal and urinary disorders
Pyuria
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60