Gastroesophageal Reflux Disease
Conditions
Keywords
Gastroesophageal Reflux Disease, GERD, Acid reflux, Compound Sodium Alginate Double Action Chewable Tablet, Gaviscon Double Action Tablets
Brief summary
This study is being conducted to assess the effectiveness of the Compound Sodium Alginate Double Action Chewable Tablets compared to placebo on acidic reflux events into the esophagus in patients diagnosed with Gastroesophageal Reflux Disease (GERD).
Interventions
DRUGSodium Alginate Double Action Chewable Tablets
4 tablets as a single dose
DRUGPlacebo
4 tablets as a single dose
Sponsors
Reckitt Benckiser Healthcare (UK) Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* meets the diagnostic criteria for GERD with a GERD history of frequent episodes of GERD-related symptoms during the last 2 months prior to study screening. The patient must also meet the following criteria: 1. The only or main symptom is heartburn (burning feeling back of breast bone) and/or acid reflux. Symptoms persist or have occurred repeatedly for more than 2 months; 2. As assessed by the Investigator at screening by questioning of the patient, the frequency of occurrence of heartburn is ≥ 3 days/week and the score of severity of heartburn in general is ≥ moderate within 3 weeks before screening
Exclusion criteria
* Patients who have a history of drug, solvent or alcohol abuse (weekly alcohol intake ≥ 140 g). * Patients who have suffered cardiac chest pain within the last year. * Patients who have suffered a recent, significant unexplained weight loss of more than 6 kg in the last 6 months. * Female patients of childbearing potential who, for the duration of the study, are either unwilling or unable to take adequate contraceptive precautions or are unwilling to be sexually abstinent. * Pregnancy or lactating mother. * Patients with a history and/or symptom profile suggestive of the following: any other gastrointestinal (GI) disease, erosive GERD (Los Angeles \[LA\] classification grades C-D), Barrett's oesophagus, acute peptic ulcer and/or ulcer complications, Zollinger-Ellison syndrome, gastric carcinoma, pyloric stenosis, oesophageal or gastric surgery, intestinal obstruction, current pernicious anaemia, indication for H. pylori eradication therapy, known gastrointestinal bleeding (hematochezia or hematemesis) within the last 3 months, and severe diseases of other major body systems. * Patients who are observed at screening to have a hiatus hernia with a diameter which exceeds 3 cm. * Patients who have taken anti-cholinesterase drugs, traditional Chinese medicines for treating gastrointestinal disease, ulcerlmin or misoprostol preparations within 7 days prior to screening or throughout the study. * Patients who have taken PPIs during the 10 days prior to screening, prokinetics or H2 antagonists during the 5 days prior to screening or systemic glucocorticosteroids, non-steroidal anti-inflammatory drugs (except for low dose aspirin which can be given for cardioprotection) on more than 3 consecutive days or PPI-based triple or quadruple therapy for eradication of H. pylori during the last 28 days. * Patients taking or requiring to take macrolide antibiotics, such as erythromycin, azithromycin, from the day before screening. * Patients with difficulty in swallowing. * Patients with known hypophosphataemia, phenylketonuria or hypercalcaemia. * Patients with severe constipation, or history of intestinal obstruction. * In the opinion of the Investigator, patients with damaged heart or kidney function and patients who require a low sodium diet.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 4 | 0 to 4 hours post-dose | The primary efficacy endpoint will be the percentage of time during the 4-hour post-dosing period with pH below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 4 | 0 to 4 hours post-dose | Number of occasions during the 4-hour post-dosing period when pH falls below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 5 | 0 to 4 hours post-dose | Number of occasions during the 4-hour post-dosing period when pH falls below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| Number of Reflux Episodes During the 4-hour Post-dosing Period With pH Below pH 4 for at Least 5 Minutes | 0 to 4 hours post-dose | Number of reflux episodes during the 4-hour post-dosing period with pH below pH 4 for at least 5 minutes for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| Percentage of Time During the First Hour Post-dosing With pH Below pH 4 | 0 to 1 hour post-dose | Percentage of time during the first hour post-dosing with pH below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 5 | 0 to 4 hours post-dose | Percentage of time during the 4-hour post-dosing period with pH below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 4 | 0 to 1 hour post-dose | Number of occasions during the first hour post-dosing when pH falls below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 5 | 0 to 1 hour post-dose | Number of occasions during the first hour post-dosing when pH falls below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| The Longest Reflux Time During the 4-hour Post-dosing Period (i.e. the Longest Period With pH Below pH 4) | 0 to 4 hours post-dose | The longest reflux time during the 4-hour post-dosing period (i.e. the longest period with pH below pH 4) for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
| The DeMeester Scores During the 4-hour Post-dosing Period | 0 to 4 hours post-dose | The DeMeester scores during the 4-hour post-dosing period for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets. The DeMeester score is a composite score of the acid exposure during a prolonged ambulatory pH monitoring. The parameters that constitute the score are number of reflux episodes, number of episodes longer than 5 minutes, longest reflux duration, total percentage of monitoring time with pH below 4, and the percentage of time with pH below 4 in an upright position and supine position, respectively. The DeMeester score is the sum of the scores calculated for each of the 6 parameters. A score more than 14.7 is considered abnormal acid reflux, scores between 14.7 and 100 are regarded as mild-to-moderate GERD, and a score greater than 100 is regarded as severe GERD. |
| Percentage of Time During the First Hour Post-dosing With pH Below pH 5 | 0 to 1 hour post-dose | Percentage of time during the first hour post-dosing with pH below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Participants in Group A received a single dose (four tablets) of Sodium Alginate Double Action Chewable Tablets at Visit 2, followed by 7 days of Compound Sodium Alginate Double Action Chewable Tablets (two tablets four times daily) and a single dose (four tablets) of Placebo tablets at Visit 3. | 22 |
| Group B Participants in Group B received a single dose (four tablets) of placebo tablets at Visit 2, followed by 7 days of Compound Sodium Alginate Double Action Chewable Tablets (two tablets four times daily) and a single dose (four tablets) of Sodium Alginate Double Action Chewable Tablets at Visit 3. | 23 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 23 Participants | 44 Participants |
| Age, Continuous | 41.6 years STANDARD_DEVIATION 15.27 | 39.3 years STANDARD_DEVIATION 16.9 | 40.4 years STANDARD_DEVIATION 15.98 |
| Race/Ethnicity, Customized Afro-Caribbean | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 22 Participants | 23 Participants | 45 Participants |
| Race/Ethnicity, Customized Caucasian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 22 participants | 23 participants | 45 participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 11 Participants | 15 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 0 / 22 | 2 / 23 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 |
Outcome results
Primary
Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 4
The primary efficacy endpoint will be the percentage of time during the 4-hour post-dosing period with pH below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 4 | 5.14 percentage of time with pH below pH 4 |
| Placebo Tablets | Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 4 | 14.94 percentage of time with pH below pH 4 |
p-value: 0.000395% CI: [-14.85, -4.74]Mixed Models Analysis
Secondary
Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 4
Number of occasions during the 4-hour post-dosing period when pH falls below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 4 | 11.5 Number of occasions pH fell below 4 |
| Placebo Tablets | Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 4 | 30.9 Number of occasions pH fell below 4 |
p-value: 0.000495% CI: [-29.6, -9.2]Mixed Models Analysis
Secondary
Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 5
Number of occasions during the 4-hour post-dosing period when pH falls below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 5 | 17.3 Number of occasions pH fell below 5 |
| Placebo Tablets | Number of Occasions During the 4-hour Post-dosing Period When pH Falls Below pH 5 | 33.6 Number of occasions pH fell below 5 |
p-value: 0.001995% CI: [-26.2, -6.4]Mixed Models Analysis
Secondary
Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 4
Number of occasions during the first hour post-dosing when pH falls below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 1 hour post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 4 | 1.7 Number of occasions pH fell below 4 |
| Placebo Tablets | Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 4 | 9.1 Number of occasions pH fell below 4 |
p-value: <0.000195% CI: [-10, -4.6]Mixed Models Analysis
Secondary
Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 5
Number of occasions during the first hour post-dosing when pH falls below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 1 hour post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 5 | 3.1 Number of occasions pH fell below 5 |
| Placebo Tablets | Number of Occasions During the First Hour Post-dosing When pH Falls Below pH 5 | 9.5 Number of occasions pH fell below 5 |
p-value: 0.000195% CI: [-9.4, -3.3]Mixed Models Analysis
Secondary
Number of Reflux Episodes During the 4-hour Post-dosing Period With pH Below pH 4 for at Least 5 Minutes
Number of reflux episodes during the 4-hour post-dosing period with pH below pH 4 for at least 5 minutes for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Number of Reflux Episodes During the 4-hour Post-dosing Period With pH Below pH 4 for at Least 5 Minutes | 0.6 Number of reflux episodes |
| Placebo Tablets | Number of Reflux Episodes During the 4-hour Post-dosing Period With pH Below pH 4 for at Least 5 Minutes | 1.4 Number of reflux episodes |
p-value: 0.02995% CI: [-1.6, -0.1]Mixed Models Analysis
Secondary
Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 5
Percentage of time during the 4-hour post-dosing period with pH below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 5 | 10.40 percentage of time with pH below pH 5 |
| Placebo Tablets | Percentage of Time During the 4-hour Post-dosing Period With pH Below pH 5 | 26.16 percentage of time with pH below pH 5 |
p-value: <0.000195% CI: [-22.82, -8.71]Mixed Models Analysis
Secondary
Percentage of Time During the First Hour Post-dosing With pH Below pH 4
Percentage of time during the first hour post-dosing with pH below pH 4 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 1 hour post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Percentage of Time During the First Hour Post-dosing With pH Below pH 4 | 2.00 percentage of time with pH below pH 4 |
| Placebo Tablets | Percentage of Time During the First Hour Post-dosing With pH Below pH 4 | 16.41 percentage of time with pH below pH 4 |
p-value: <0.000195% CI: [-20.57, -8.23]Mixed Models Analysis
Secondary
Percentage of Time During the First Hour Post-dosing With pH Below pH 5
Percentage of time during the first hour post-dosing with pH below pH 5 for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 1 hour post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | Percentage of Time During the First Hour Post-dosing With pH Below pH 5 | 4.23 percentage of time with pH below pH 5 |
| Placebo Tablets | Percentage of Time During the First Hour Post-dosing With pH Below pH 5 | 27.60 percentage of time with pH below pH 5 |
p-value: <0.000195% CI: [-31.55, -15.19]Mixed Models Analysis
Secondary
The DeMeester Scores During the 4-hour Post-dosing Period
The DeMeester scores during the 4-hour post-dosing period for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets. The DeMeester score is a composite score of the acid exposure during a prolonged ambulatory pH monitoring. The parameters that constitute the score are number of reflux episodes, number of episodes longer than 5 minutes, longest reflux duration, total percentage of monitoring time with pH below 4, and the percentage of time with pH below 4 in an upright position and supine position, respectively. The DeMeester score is the sum of the scores calculated for each of the 6 parameters. A score more than 14.7 is considered abnormal acid reflux, scores between 14.7 and 100 are regarded as mild-to-moderate GERD, and a score greater than 100 is regarded as severe GERD.
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | The DeMeester Scores During the 4-hour Post-dosing Period | 14.842 score on a scale |
| Placebo Tablets | The DeMeester Scores During the 4-hour Post-dosing Period | 38.987 score on a scale |
p-value: 0.000795% CI: [-37.432, -10.858]Mixed Models Analysis
Secondary
The Longest Reflux Time During the 4-hour Post-dosing Period (i.e. the Longest Period With pH Below pH 4)
The longest reflux time during the 4-hour post-dosing period (i.e. the longest period with pH below pH 4) for Compound Sodium Alginate Double Action Chewable Tablets versus matching placebo tablets
Time frame: 0 to 4 hours post-dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Alginate Double Action Chewable Tablets | The Longest Reflux Time During the 4-hour Post-dosing Period (i.e. the Longest Period With pH Below pH 4) | 3.3 minutes |
| Placebo Tablets | The Longest Reflux Time During the 4-hour Post-dosing Period (i.e. the Longest Period With pH Below pH 4) | 9.6 minutes |
p-value: 0.007595% CI: [-10.9, -1.8]Mixed Models Analysis