Heartburn
Conditions
Brief summary
The purpose of this pilot study is to investigate the association between gastric acid suppression and relief of 24 hour heartburn following treatment with the proton pump inhibitor (PPI) drug esomeprazole in frequent heartburn patients.
Interventions
Esomeprazole 20 mg banded capsules (22.3 mg esomeprazole magnesium trihydrate)
DRUGPlacebo
Placebo capsules
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed symptom history of heartburn, acid regurgitation, or epigastric pain of at least 3 months, while treating with gastric acid modulating therapy (antacids, H2 receptor antagonists (H2RAs) and/or PPIs). * Heartburn symptoms that average 3 times per week or greater including at least 2 episodes of nighttime heartburn symptoms per week over the past 30 days. * When heartburn medications were used, subject had heartburn symptoms that were responsive to antacids, non prescription H2RAs, or short term non prescription or prescription PPIs at approved doses but complete resolution of heartburn was not achieved.
Exclusion criteria
* A history (past or present) of erosive esophagitis verified by endoscopy. * The need for continuous treatment with H2RAs, PPIs, gastric prokinetic drugs, or antacids for any indication through the study (eg, long term prescription therapy). * Subjects requiring continuous intervention by a physician for the treatment of GERD (ie, treatment of erosive esophagitis or prevention of relapse of healed esophagitis).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | Day 8 up to Day 14 | Relief of 24 hour heartburn was defined as a daily diary response of 0 to the question Over the last 24 hours (yesterday and last night), what was the severity of your most intense episode of heartburn? on at least 6 of the participant's last 7 consecutive days \[Days 8 - 14\] of treatment allowing for one day with a maximum severity of 2.The response was noted by participants in the diary for last 7 consecutive days \[Day 8 - 14\] on a 3 point scale ranged from 0 to 2 where 0= complete relief and 2= maximum severity. Higher score indicated worse condition/more severity. In this outcome measure, participants with relief of 24 hour heartburn and participants without relief of 24 hour heartburn were reported. |
| Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Baseline, Day 14 | Percentage of time was calculated over the 24 hour period during which intra gastric pH \>4 was observed. Relief of 24 hour heartburn was defined as a daily diary response of 0 to the question Over the last 24 hours (yesterday and last night), what was the severity of your most intense episode of heartburn? on at least 6 of the participant's last 7 consecutive days \[Days 8 - 14\] of treatment allowing for one day with a maximum severity of 2.The response was noted by participants in the diary for last 7 consecutive days \[Day 8 - 14\] on a 3 point scale ranged from 0 to 2 where 0= complete relief and 2= maximum severity. Higher score indicated worse condition/more severity. In this outcome, change from baseline at Day 14 in percentage of time over the 24 hour period during which intra gastric pH \>4 was observed, was reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole 20 mg Twice Daily Esomeprazole 20 milligram capsules administered orally twice daily from Day 1 to 14. | 21 |
| Esomeprazole 20 mg Once Daily + Placebo Esomeprazole 20 mg capsule administered orally once daily in the morning and placebo matched to esomeprazole capsule once daily in the evening from Day 1 to 14. | 22 |
| Placebo Placebo matched to esomeprazole capsules administered orally twice daily from Day 1 to 14. | 12 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Esomeprazole 20 mg Twice Daily | Esomeprazole 20 mg Once Daily + Placebo | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 10.23 | 40.8 years STANDARD_DEVIATION 10.95 | 44.7 years STANDARD_DEVIATION 10.5 | 41.9 years STANDARD_DEVIATION 10.49 |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 9 Participants | 34 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 3 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 21 | 1 / 22 | 2 / 12 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 | 0 / 12 |
Outcome results
Primary
Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4
Percentage of time was calculated over the 24 hour period during which intra gastric pH \>4 was observed. Relief of 24 hour heartburn was defined as a daily diary response of 0 to the question Over the last 24 hours (yesterday and last night), what was the severity of your most intense episode of heartburn? on at least 6 of the participant's last 7 consecutive days \[Days 8 - 14\] of treatment allowing for one day with a maximum severity of 2.The response was noted by participants in the diary for last 7 consecutive days \[Day 8 - 14\] on a 3 point scale ranged from 0 to 2 where 0= complete relief and 2= maximum severity. Higher score indicated worse condition/more severity. In this outcome, change from baseline at Day 14 in percentage of time over the 24 hour period during which intra gastric pH \>4 was observed, was reported.
Time frame: Baseline, Day 14
Population: Per protocol analysis set included all randomized participants who provided valid data for Day -1 PH monitoring, take at least one dose of randomized study medication, complete the 14 day treatment phase, undergo and provide valid data for Day 14 pH monitoring and complete at least 5 days of diary entries in each of Days -7 to -1 and Days 8 to 14.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Esomeprazole 20 mg Twice Daily | Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Baseline | 12.53 percentage of time | Standard Deviation 18.045 |
| Esomeprazole 20 mg Twice Daily | Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Change at Day 14 | 70.23 percentage of time | Standard Deviation 23.105 |
| Esomeprazole 20 mg Once Daily + Placebo | Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Baseline | 13.35 percentage of time | Standard Deviation 9.069 |
| Esomeprazole 20 mg Once Daily + Placebo | Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Change at Day 14 | 42.83 percentage of time | Standard Deviation 18.654 |
| Placebo | Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Baseline | 12.32 percentage of time | Standard Deviation 5.635 |
| Placebo | Change From Baseline at Day 14 in Percentage of Time Over 24--Hour Period With Intra Gastric pH Greater Than (>)4 | Change at Day 14 | 0.78 percentage of time | Standard Deviation 5.839 |
Comparison: Association between percentage of time with intragastric pH\>4 and relief of 24 -hour heartburn was assessed using logistic regression model with relief of 24- hour heartburn at Day 14 as dependent variable and change in percentage of time with intragastric pH\>4 as the independent variable, controlling for age, sex, and body mass index (BMI).p-value: 0.044295% CI: [1.001, 1.055]Regression, Logistic
Primary
Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn
Relief of 24 hour heartburn was defined as a daily diary response of 0 to the question Over the last 24 hours (yesterday and last night), what was the severity of your most intense episode of heartburn? on at least 6 of the participant's last 7 consecutive days \[Days 8 - 14\] of treatment allowing for one day with a maximum severity of 2.The response was noted by participants in the diary for last 7 consecutive days \[Day 8 - 14\] on a 3 point scale ranged from 0 to 2 where 0= complete relief and 2= maximum severity. Higher score indicated worse condition/more severity. In this outcome measure, participants with relief of 24 hour heartburn and participants without relief of 24 hour heartburn were reported.
Time frame: Day 8 up to Day 14
Population: Per protocol analysis set included all randomized participants who provided valid data for Day -1 PH monitoring, take at least one dose of randomized study medication, complete the 14 day treatment phase, undergo and provide valid data for Day 14 pH monitoring and complete at least 5 days of diary entries in each of Days -7 to -1 and Days 8 to 14.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Esomeprazole 20 mg Twice Daily | Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | With Relief | 7 participants |
| Esomeprazole 20 mg Twice Daily | Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | Without Relief | 9 participants |
| Esomeprazole 20 mg Once Daily + Placebo | Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | With Relief | 10 participants |
| Esomeprazole 20 mg Once Daily + Placebo | Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | Without Relief | 8 participants |
| Placebo | Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | With Relief | 0 participants |
| Placebo | Number of Participants With Relief of 24 Hour Heartburn and Without Relief of 24 Hour Heartburn | Without Relief | 5 participants |