Reflux
Conditions
Keywords
Pharmacodynamic effect, Reflux inhibition
Brief summary
The purpose of this study is to investigate the pharmacodynamic effect of AZD2516 in healthy male subjects.
Detailed description
A double-blind, randomized, placebo-controlled, two-centre, phase IIa pharmacodynamic cross-over study to assess the effect of AZD2516 on the total number of reflux episodes in healthy male volunteers.
Interventions
DRUGAZD2516, 5 mg
Capsule, oral
DRUGAZD2516, 16 mg
Capsule, oral
DRUGAZD2516, 40 mg
Capsule, oral
DRUGPlacebo
Capsule, oral
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed informed consent * Healthy male subjects * Age 18-45 years, inclusive
Exclusion criteria
* Clinically significant illness within the 2 weeks prior to the first dose of study drug * History of clinically significant cardiovascular, respiratory, renal, hepatic, neurological, mental or gastrointestinal disease * Need for concomitant medications during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reflux Episodes 0 to 3 Hours Post Meal | 0 to 3 hours post meal | Total number of reflux episodes 0 to 3 hours post meal |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Curve(AUC) | 0 to 12 hours post dose | Area under the plasma concentration vs. time curve from time zero to 12-hours post dose calculated by loglinear trapezoidal method |
| Average Plasma Concentration (C Average) | 1 to 4 hours post dose | Average plasma concentration |
| Maximum Plasma Concentration (Cmax) | 0 to 12 hours post dose | Maximum plasma concentration |
| Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal | 0 to 3 hours post meal | Number of TLESRs 0 to 3 hours post meal were calculated based upon the manometric analysis fpr the 3-hour post-meal period. |
| Terminal Half-life (T Half) | 0 to 12 hours post dose | Terminal half-life (T half) |
| Clinically Relevant Change of Laboratory Variables | Pre-entry to follow-up | Number of participants with clinically relevant change of laboratory variables as judged by the responsible medical officer. |
| Time to Maximum Plasma Concentration (Tmax) | 0 to 12 hours post dose | Time to maximum plasma concentration (Tmax) |
Countries
Belgium, Netherlands
Participant flow
Recruitment details
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.
Pre-assignment details
After enrolment, participant's eligibility for assignment to treatment was based on inclusion and exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| AZD2516 5 mg 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. | 4 |
| AZD2516 16 mg Loading dose: 2 \* AZD2516 5mg capsule, 1 \* placebo capsule. Maintenance dose: 3 \* AZD2516 1 mg capsule and 3 \* AZD2516 1 mg capsule. | 7 |
| AZD2516 40 mg 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. | 4 |
| Placebo Loading dose: 3 \* placebo capsules. Maintenance dose: 3 \* placebo capsules and 3 \* placebo capsules. | 5 |
| Total | 20 |
Baseline characteristics
| Characteristic | AZD2516 5 mg | AZD2516 16 mg | AZD2516 40 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous Age (years) | 31 years STANDARD_DEVIATION 9.6 | 25 years STANDARD_DEVIATION 4.5 | 28.8 years STANDARD_DEVIATION 5.9 | 23 years STANDARD_DEVIATION 4.2 | 26.95 years STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 4 Participants | 5 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 20 | 8 / 20 | 12 / 20 | 3 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Reflux Episodes 0 to 3 Hours Post Meal
Total number of reflux episodes 0 to 3 hours post meal
Time frame: 0 to 3 hours post meal
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2516 5 mg | Reflux Episodes 0 to 3 Hours Post Meal | 15.1 Episodes |
| AZD2516 16 mg | Reflux Episodes 0 to 3 Hours Post Meal | 12.5 Episodes |
| AZD2516 40 mg | Reflux Episodes 0 to 3 Hours Post Meal | 11.0 Episodes |
| Placebo | Reflux Episodes 0 to 3 Hours Post Meal | 12.7 Episodes |
Secondary
Area Under the Plasma Concentration Curve(AUC)
Area under the plasma concentration vs. time curve from time zero to 12-hours post dose calculated by loglinear trapezoidal method
Time frame: 0 to 12 hours post dose
Population: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2516 5 mg | Area Under the Plasma Concentration Curve(AUC) | 251.5 nmol*h/L |
| AZD2516 16 mg | Area Under the Plasma Concentration Curve(AUC) | 906.6 nmol*h/L |
| AZD2516 40 mg | Area Under the Plasma Concentration Curve(AUC) | 2825 nmol*h/L |
Secondary
Average Plasma Concentration (C Average)
Average plasma concentration
Time frame: 1 to 4 hours post dose
Population: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2516 5 mg | Average Plasma Concentration (C Average) | 45.46 nmol/L |
| AZD2516 16 mg | Average Plasma Concentration (C Average) | 175.8 nmol/L |
| AZD2516 40 mg | Average Plasma Concentration (C Average) | 506.8 nmol/L |
Secondary
Clinically Relevant Change of Laboratory Variables
Number of participants with clinically relevant change of laboratory variables as judged by the responsible medical officer.
Time frame: Pre-entry to follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2516 5 mg | Clinically Relevant Change of Laboratory Variables | 0 Participants |
| AZD2516 16 mg | Clinically Relevant Change of Laboratory Variables | 0 Participants |
| AZD2516 40 mg | Clinically Relevant Change of Laboratory Variables | 0 Participants |
| Placebo | Clinically Relevant Change of Laboratory Variables | 0 Participants |
Secondary
Maximum Plasma Concentration (Cmax)
Maximum plasma concentration
Time frame: 0 to 12 hours post dose
Population: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2516 5 mg | Maximum Plasma Concentration (Cmax) | 103.8 nmol/L |
| AZD2516 16 mg | Maximum Plasma Concentration (Cmax) | 378.0 nmol/L |
| AZD2516 40 mg | Maximum Plasma Concentration (Cmax) | 911.7 nmol/L |
Secondary
Terminal Half-life (T Half)
Terminal half-life (T half)
Time frame: 0 to 12 hours post dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2516 5 mg | Terminal Half-life (T Half) | 1.221 hours |
| AZD2516 16 mg | Terminal Half-life (T Half) | 1.416 hours |
| AZD2516 40 mg | Terminal Half-life (T Half) | 1.584 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax)
Time to maximum plasma concentration (Tmax)
Time frame: 0 to 12 hours post dose
Population: Data from one subject in arm AZD2516 5 mg were excluded from efficacy analysis due to incorrect medication received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD2516 5 mg | Time to Maximum Plasma Concentration (Tmax) | 0.750 hours |
| AZD2516 16 mg | Time to Maximum Plasma Concentration (Tmax) | 0.750 hours |
| AZD2516 40 mg | Time to Maximum Plasma Concentration (Tmax) | 1.000 hours |
Secondary
Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal
Number of TLESRs 0 to 3 hours post meal were calculated based upon the manometric analysis fpr the 3-hour post-meal period.
Time frame: 0 to 3 hours post meal
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2516 5 mg | Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal | 16.9 relaxations |
| AZD2516 16 mg | Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal | 16.2 relaxations |
| AZD2516 40 mg | Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal | 10.4 relaxations |
| Placebo | Transient Lower Esophagus Sphincter Relaxations (TLESRs) 0 to 3 Hours Post Meal | 16.8 relaxations |