Gastroesophageal Reflux Disease
Conditions
Keywords
GERD, lesogaberan, impedance, pH, pharmacokinetics, safety, tolerability
Brief summary
The purpose of the study is to estimate what effect 4 different doses of AZD3355 will have on the number of reflux episodes, in patients who have GERD and still experience symptoms despite proton pump inhibitor (PPI) treatment.
Interventions
DRUGAZD3355
30 mg orally in the morning and 30 mg in the evening for 1 day
DRUGplacebo
Placebo capsules orally in the morning and placebo capsules in the evening for 1 day
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Provide informed consent * History of GERD with persistent symptoms despite treatment with PPI * Otherwise normal physical health
Exclusion criteria
* History of GERD with symptoms that has not improved at all during treatment with PPI * Prior surgery of the upper gastrointestinal tract * History of significant heart disease, cardiovascular, respiratory, hepatic, renal, metabolic, psychiatric or gastrointestinal disorders besides GERD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Reflux Episodes During 24 Hours | Measured during 24 hours at 4 different visits with a 7-28 days interval between | Number of reflux episodes assessed during ambulatory impedance-pH recording (defined as starting with a drop in impedance to below 50% of baseline and ending when impedance recovers to above 50% of baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Acid Reflux Episodes | Measured during 24 hours at 4 different visits with a 7-28 days interval between | Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH \<4 (or a drop of at least 1 pH unit if pH is already \<4) lasting more than 5 s. |
| Number of Weakly Acidic Reflux Episodes | Measured during 24 hours at 4 different visits with a 7-28 days interval between | Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH 4.0-6.5 lasting more than 5 s. |
| Number of Weakly Alkaline Reflux Episodes | Measured during 24 hours at 4 different visits with a 7-28 days interval between | Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH ≥6.5 lasting more than 5 s. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all groups randomized to one of 10 sequences of drug or placebo. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 6 - Third Washout Period | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 43.3 Years |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 1 / 21 | 0 / 21 | 3 / 20 | 2 / 26 |
| serious Total, serious adverse events | 0 / 19 | 0 / 21 | 0 / 21 | 1 / 20 | 0 / 26 |
Outcome results
Primary
Total Number of Reflux Episodes During 24 Hours
Number of reflux episodes assessed during ambulatory impedance-pH recording (defined as starting with a drop in impedance to below 50% of baseline and ending when impedance recovers to above 50% of baseline)
Time frame: Measured during 24 hours at 4 different visits with a 7-28 days interval between
Population: Efficacy Analysis Set (EAS). From the safety analysis set with 27 patients, the EAS excludes 2 patients; 1 due to a positive drug of abuse screen and 1 due to poor quality of the impedance/pH tracings during all 4 study periods. Additionally, 3 patients were partly excluded from the EAS due to poor quality of the tracings during 1 study period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3355 30 mg | Total Number of Reflux Episodes During 24 Hours | 59.4 Episodes |
| AZD3355 90 mg | Total Number of Reflux Episodes During 24 Hours | 50.7 Episodes |
| AZD3355 120 mg | Total Number of Reflux Episodes During 24 Hours | 44.3 Episodes |
| AZD3355 240 mg | Total Number of Reflux Episodes During 24 Hours | 38.0 Episodes |
| Placebo | Total Number of Reflux Episodes During 24 Hours | 80.5 Episodes |
Secondary
Number of Acid Reflux Episodes
Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH \<4 (or a drop of at least 1 pH unit if pH is already \<4) lasting more than 5 s.
Time frame: Measured during 24 hours at 4 different visits with a 7-28 days interval between
Population: Efficacy Analysis Set (EAS). From the safety analysis set with 27 patients, the EAS excludes 2 patients; 1 due to a positive drug of abuse screen and 1 due to poor quality of the impedance/pH tracings during all 4 study periods. Additionally, 3 patients were partly excluded from the EAS due to poor quality of the tracings during 1 study period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3355 30 mg | Number of Acid Reflux Episodes | 9.6 Episodes |
| AZD3355 90 mg | Number of Acid Reflux Episodes | 8.0 Episodes |
| AZD3355 120 mg | Number of Acid Reflux Episodes | 6.2 Episodes |
| AZD3355 240 mg | Number of Acid Reflux Episodes | 6.3 Episodes |
| Placebo | Number of Acid Reflux Episodes | 14.7 Episodes |
Secondary
Number of Weakly Acidic Reflux Episodes
Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH 4.0-6.5 lasting more than 5 s.
Time frame: Measured during 24 hours at 4 different visits with a 7-28 days interval between
Population: Efficacy Analysis Set (EAS). From the safety analysis set with 27 patients, the EAS excludes 2 patients; 1 due to a positive drug of abuse screen and 1 due to poor quality of the impedance/pH tracings during all 4 study periods. Additionally, 3 patients were partly excluded from the EAS due to poor quality of the tracings during 1 study period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3355 30 mg | Number of Weakly Acidic Reflux Episodes | 37.0 Episodes |
| AZD3355 90 mg | Number of Weakly Acidic Reflux Episodes | 35.4 Episodes |
| AZD3355 120 mg | Number of Weakly Acidic Reflux Episodes | 28.7 Episodes |
| AZD3355 240 mg | Number of Weakly Acidic Reflux Episodes | 28.4 Episodes |
| Placebo | Number of Weakly Acidic Reflux Episodes | 51.6 Episodes |
Secondary
Number of Weakly Alkaline Reflux Episodes
Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH ≥6.5 lasting more than 5 s.
Time frame: Measured during 24 hours at 4 different visits with a 7-28 days interval between
Population: Efficacy Analysis Set (EAS). From the safety analysis set with 27 patients, the EAS excludes 2 patients; 1 due to a positive drug of abuse screen and 1 due to poor quality of the impedance/pH tracings during all 4 study periods. Additionally, 3 patients were partly excluded from the EAS due to poor quality of the tracings during 1 study period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD3355 30 mg | Number of Weakly Alkaline Reflux Episodes | 0 Episodes |
| AZD3355 90 mg | Number of Weakly Alkaline Reflux Episodes | 0 Episodes |
| AZD3355 120 mg | Number of Weakly Alkaline Reflux Episodes | 0 Episodes |
| AZD3355 240 mg | Number of Weakly Alkaline Reflux Episodes | 0 Episodes |
| Placebo | Number of Weakly Alkaline Reflux Episodes | 0 Episodes |