Reflux Episodes
Conditions
Keywords
GERD, transient lower esophageal sphincter relaxations (TLESRs), reflux
Brief summary
The purpose of the study is to compare frequency and content of reflux episodes in patients with gastroesophageal reflux disease.
Interventions
DRUGAZD3355
65 mg capsules, oral, 3 single doses
DRUGPlacebo
capsules, oral, 3 single doses
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written consent * GERD patients, age 18-70 years, females must be postmenopausal or surgically sterilised * 6 months history of GERD and incomplete response to PPI treatment
Exclusion criteria
* Insufficient symptom burden of the reflux disease evaluated by questionnaires * S-creatinine \>1.2 times upper limit of normal * History of heart disease * Prior surgery of the upper GI tract
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose | 0-3 hours post meal, post third dose | The number of relaxations for each patient in each period was determined from manometric tracings according to previously published criteria (R.H. Holloway, R. Penagini and A.C. Ireland, Criteria for objective definition of transient lower esophageal sphincter relaxation, Am J Physiol 268 (1995), pp. G128-G133). The analysis of the number of TLESRs was based on an analysis of variance (ANOVA) for log-transformed data. The 95% level confidence interval (CI) limits were transformed back to the original scale to give CIs for the geometric mean for each treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number Reflux Episodes 0-24 Hours Post First Dose | 0-24 hours | Number of reflux episodes assessed during the 24-hour ambulatory impedance-pH recording. |
| Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method. | 0-12 hours post first dose | The AUCtau was calculated for each patient in the period with AZD3355 treatment by the Log-Linear Trapezoidal Method. The descriptive geometric mean of the individual AUCtau values is reported here. |
Participant flow
Recruitment details
42 patients in 2 countries were enrolled in the study. 27 patients were randomised to treatment. 2 patients discontinued prematurely, 1 due to low Lower Esophageal Sphincter Pressure (LESP)/catheter placement problems, and 1 due to nausea/vomiting. Thus, 25 patients completed the study, 10 in Belgium and 15 in the Netherlands.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to received Drug first and Placebo first. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Catheter placement problems | 0 | 1 |
| Washout Period | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 51.6 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 25 | 18 / 27 |
| serious Total, serious adverse events | 0 / 25 | 0 / 27 |
Outcome results
Primary
Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose
The number of relaxations for each patient in each period was determined from manometric tracings according to previously published criteria (R.H. Holloway, R. Penagini and A.C. Ireland, Criteria for objective definition of transient lower esophageal sphincter relaxation, Am J Physiol 268 (1995), pp. G128-G133). The analysis of the number of TLESRs was based on an analysis of variance (ANOVA) for log-transformed data. The 95% level confidence interval (CI) limits were transformed back to the original scale to give CIs for the geometric mean for each treatment.
Time frame: 0-3 hours post meal, post third dose
Population: Per Protocol Analysis Set (PP). From the safety analysis set with 27 patients, the PP excludes 2 patients since they discontinued prematurely from the study. Additionally, 4 patients were excluded from the primary analysis; 1 due to catheter placement problems, 1 due to error in dose administration, 1 due to low LESP, 1 due to multiple swallowing.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3355 | Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose | 11.6 Relaxations |
| Placebo | Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose | 15.5 Relaxations |
Secondary
Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method.
The AUCtau was calculated for each patient in the period with AZD3355 treatment by the Log-Linear Trapezoidal Method. The descriptive geometric mean of the individual AUCtau values is reported here.
Time frame: 0-12 hours post first dose
Population: Per Protocol Analysis Set (PP). From the safety analysis set with 27 patients, the PP excludes 2 patients since they discontinued prematurely from the study. Additionally, 1 patient was excluded from the pharmacokinetic analysis due to error in dose administration at dose 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD3355 | Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method. | 7.16 μmol*hours / L | Standard Deviation 2.36 |
Secondary
Total Number Reflux Episodes 0-24 Hours Post First Dose
Number of reflux episodes assessed during the 24-hour ambulatory impedance-pH recording.
Time frame: 0-24 hours
Population: Per Protocol Analysis Set (PP). From the safety analysis set with 27 patients, the PP excludes 2 patients since they discontinued prematurely from the study. Additionally, 4 patients were excluded from this analysis; 1 due to catheter placement problems, 1 due to error in dose administration, 2 due to insufficient impedance/pH recording time.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3355 | Total Number Reflux Episodes 0-24 Hours Post First Dose | 30.6 Episodes |
| Placebo | Total Number Reflux Episodes 0-24 Hours Post First Dose | 50.5 Episodes |