Gastroesophageal Reflux
Conditions
Keywords
Gastroesophageal Reflux, Gastroesophageal Reflux Disease, GERD, Proton Pump Inhibitor, PPI, Regurgitation, Infants, AcipHex, PARIET, ALFENCE
Brief summary
The purpose of this study is to assess the effectiveness and safety of rabeprazole sodium, an inhibitor of gastric acid secretion of the protein pump inhibitor (PPI) class, compared with placebo in the treatment of gastrointestinal esophageal reflux disease (GERD) in infants 1 to 11 months of age.
Detailed description
Rabeprazole sodium belongs to the class of drugs known as proton pump inhibitors, which suppress gastric acid secretion. The drug is approved in the United States for the treatment of adults with GERD and other acid-related gastrointestinal disorders, and has been studied in adolescents (older than 12 years of age) with results similar to those in adults. However, the drug has not been studied in children under the age of 12 years. This study focuses on the efficacy and safety of rabeprazole sodium in infants aged 1 to 11 months, the pediatric group in which the prevalence of GERD-related symptoms is the greatest. This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group withdrawal study to compare the efficacy and safety of 2 doses (0.5 mg/kg or 1.0 mg/kg daily) of rabeprazole with placebo in the treatment of infants aged 1 to 11 months who have a diagnosis of suspected GERD, symptomatic GERD, or endoscopically or histologically proven GERD. The study consists of 3 study periods: a screening period of up to 10 days, an open-label treatment period of up to 3 weeks, and a 5-week double-blind treatment period. Patients who have been receiving GERD therapy before screening will have their GERD therapy discontinued for 3 days before entering the open-label treatment period. Patients who have a positive clinical response according to the Clinical Global Impressions - Improvement (CGI-I) scale at the end of the first or second week of the open-label treatment period will enter the double-blind treatment period; those who do not will be withdrawn from the study. A parent, legal guardian, or other individual experienced in the care of the infant will be the primary caregiver, who is responsible for the daily and weekly assessments and study drug administration. Efficacy assessments consist of the Infant Gastroesophageal Reflux Questionnaire Revised (I GERQ-R) total score, the Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I GERQ-DD) total score, the CGI-I, the Global Treatment Satisfaction Score, and the weight-for-age Z-score. Safety assessments include monitoring of concomitant therapies and adverse events throughout the study; clinical laboratory testing (hematology, clinical chemistry, urinalysis), measurement of vital signs (pulse and respiratory rate, blood pressure, temperature); and physical examination including length and weight. The study hypothesis is that rabeprazole sodium is superior to placebo in the treatment of GERD in infants aged 1 to 11 months. Rabeprazole sodium capsule(s) by mouth once a day, 10.0 milligram (mg)/kilogram (kg) for up to 3 weeks during the open-label treatment period and either 5.0 mg/kg or 10.0 mg/kg during the 5-week double-blind treatment period. To give the study drug to the infants, the contents of the capsule(s) are sprinkled onto a small amount of soft food or, as needed, the contents of the capsule(s) may be given in a small amount (5 milliliter \[mL\]) of infant formula or expressed breast milk.
Interventions
Rabeprazole Sodium 5 mg capsules once daily in the morning.
Rabeprazole Sodium 10 mg capsules once daily in the morning.
DRUGPlacebo
Matching placebo capsules once daily in the morning.
Sponsors
Eisai Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Months to 11 Months
Healthy volunteers
No
Inclusion criteria
* Diagnosis of suspected GERD, symptomatic GERD, or endoscopically or histologically proven GERD, based on frequent vomiting or regurgitation, with at least 1 of the following: a) poor weight gain, or b) irritability, excessive crying or disturbed sleep that both the parent(s) and the doctor consider abnormal (but not due to colic) * or c) refusal to eat even if hungry or arching of the back during meals * weight 2.5 kg to 15.0 kg * I-GERQ-R score \>16 * Have only 1 caregiver in addition to the parent(s)
Exclusion criteria
* History of confirmed acute life-threatening events due to GERD * Known narrowing of the opening from the stomach to the small intestines * Confirmed diagnosis of cow's milk allergy * Have taken PPIs or H2-blockers (a class of drugs that inhibit stomach acid production) or any of several drugs that affect the normal movement of the digestive tract (caffeine, theophylline, antacids, erythromycin, and others) within 3 days before entering the study * Have blood or urine test results that are well above or below the normal range for the infant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | Baseline, Week 8 | The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the participant has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. Each of the 9 items will be assigned a numeric score. The total score will be calculated as the sum of all 9 items, and ranges from 0 to 37. A higher value indicates a worse outcome. |
| Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward) | Baseline, Week 8 | — |
| Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward) | Baseline, Week 8 | Body weight was measured with the participant unclothed and before a feeding during each office visit. In the analysis of weight data, weight will be transformed to the weight-for-age Z-score using World Health Organization Child Growth Standards, taking into account the infant's age and gender (Borghi E, 2006). |
| Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | Baseline, Week 8 | The Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) is a 12-item questionnaire that is completed by the primary caregiver at every office or telephonic visit. It has a weekly recall and the items cover the frequency, amount and discomfort attributed to spit-up, refusal or stopping feeding, crying and fussing, hiccups, arching back and stopping breathing or changing color. The total score is calculated as the sum of all 12 scores for the individual questions, and ranges from 0 to 42. A higher value indicates a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Baseline, Week 8 | — |
| Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | Baseline, Week 8 | The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the participant has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. The Regurgitation subscale will be calculated as the sum of the 3 questions regarding regurgitation (Questions 1, 2, 3) and will range from 0 to 13. For each subscale score, a higher value indicates a worse outcome. |
| Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | Baseline, Week 8 | The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the subject has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. The Discomfort subscale score will be calculated as the sum of the 3 questions regarding discomfort (Questions, 7, 8, 9) and will range from 0 to 12. For each subscale score, a higher value indicates a worse outcome. |
| Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | Baseline, Week 8 | The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the subject has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. The Eating Behavior subscale score will be calculated as the sum of the 3 questions regarding eating behavior (Questions 4, 5, 6) and will range from 0 to 12. For each subscale score, a higher value indicates a worse outcome. |
Countries
Australia, Belgium, Bulgaria, Denmark, Hungary, Israel, Netherlands, Poland, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Rabeprazole Sodium 10 mg Rabeprazole Sodium capsules once daily in the morning. | 344 |
| Total | 344 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Phase | Adverse Event | 0 | 6 | 2 | 3 |
| Double-Blind Phase | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Double-Blind Phase | Other | 0 | 1 | 6 | 3 |
| Double-Blind Phase | Withdrawal by Subject | 0 | 6 | 5 | 2 |
| Open-Label Phase | Adverse Event | 4 | 0 | 0 | 0 |
| Open-Label Phase | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Open-Label Phase | Other | 45 | 0 | 0 | 0 |
| Open-Label Phase | Physician Decision | 4 | 0 | 0 | 0 |
| Open-Label Phase | Protocol Violation | 3 | 0 | 0 | 0 |
| Open-Label Phase | Withdrawal by Subject | 20 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Open-Label Rabeprazole Sodium 10 mg |
|---|---|
| AgeCategorical >= 1 to < 4 Months | 175 participants |
| AgeCategorical >= 4 to < 8 Months | 124 participants |
| AgeCategorical >= 8 to < 12 Months | 45 participants |
| Age Continuous | 4.6 months STANDARD_DEVIATION 2.55 |
| Region of Enrollment AUSTRALIA | 7 participants |
| Region of Enrollment BELGIUM | 11 participants |
| Region of Enrollment BULGARIA | 24 participants |
| Region of Enrollment HUNGARY | 51 participants |
| Region of Enrollment ISRAEL | 36 participants |
| Region of Enrollment ITALY | 5 participants |
| Region of Enrollment NETHERLANDS | 9 participants |
| Region of Enrollment POLAND | 56 participants |
| Region of Enrollment SOUTH AFRICA | 12 participants |
| Region of Enrollment UNITED STATES | 133 participants |
| Sex: Female, Male Female | 139 Participants |
| Sex: Female, Male Male | 205 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 | 116 / 344 | 33 / 89 | 34 / 90 | 32 / 88 |
| serious Total, serious adverse events | 15 / 344 | 2 / 89 | 8 / 90 | 3 / 88 |
Outcome results
Primary
Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward)
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward) | -0.8 frequency of Regurgitation | Standard Deviation 1.58 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward) | -0.8 frequency of Regurgitation | Standard Deviation 1.55 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward) | -1.6 frequency of Regurgitation | Standard Deviation 3.63 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in Average Daily Frequency of Regurgitation (Double-blind Phase/ Baseline Observation Carried Forward) | -1.2 frequency of Regurgitation | Standard Deviation 2.79 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Change from Open-label (OL) Baseline to OL Endpoint as covariate to test the hypothesis of no difference in change in daily average frequency of regurgitation from Double-blind (DB) Baseline to DB Endpoint between rabeprazole sodium total and placebo.p-value: 0.16895% CI: [-1.087, 0.19]ANCOVA
Primary
Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward)
The Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) is a 12-item questionnaire that is completed by the primary caregiver at every office or telephonic visit. It has a weekly recall and the items cover the frequency, amount and discomfort attributed to spit-up, refusal or stopping feeding, crying and fussing, hiccups, arching back and stopping breathing or changing color. The total score is calculated as the sum of all 12 scores for the individual questions, and ranges from 0 to 42. A higher value indicates a worse outcome.
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -3.6 scores on a scale | Standard Deviation 6.41 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -3.8 scores on a scale | Standard Deviation 7.5 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -4.1 scores on a scale | Standard Deviation 7 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in I-GERQ-R Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -3.9 scores on a scale | Standard Deviation 7.24 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Change from Open-label (OL) Baseline to OL Endpoint as covariate to test the hypothesis of no difference in change in I-GERQ-R Total Score from Double-blind (DB) Baseline to DB Endpoint between rabeprazole sodium total and placebo.p-value: 0.9695% CI: [-1.615, 1.7]ANCOVA
Primary
Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward)
The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the participant has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. Each of the 9 items will be assigned a numeric score. The total score will be calculated as the sum of all 9 items, and ranges from 0 to 37. A higher value indicates a worse outcome.
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -1.9 scores on a scale | Standard Deviation 4.55 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -1.6 scores on a scale | Standard Deviation 4.85 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -2.1 scores on a scale | Standard Deviation 4.9 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in in Weekly Average I-GERQ-DD Total Score (Double-blind Phase/ Baseline Observation Carried Forward) | -1.9 scores on a scale | Standard Deviation 4.86 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Change from Open-label (OL) Baseline to OL Endpoint as covariate to test the hypothesis of no difference in change in Weekly Average I-GERQ-DD Total Score from Double-blind (DB) Baseline to DB Endpoint between rabeprazole sodium total and placebo.p-value: 0.96895% CI: [-1.167, 1.214]ANCOVA
Primary
Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward)
Body weight was measured with the participant unclothed and before a feeding during each office visit. In the analysis of weight data, weight will be transformed to the weight-for-age Z-score using World Health Organization Child Growth Standards, taking into account the infant's age and gender (Borghi E, 2006).
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward) | 0.11 Z-score | Standard Deviation 0.329 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward) | 0.16 Z-score | Standard Deviation 0.322 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward) | 0.11 Z-score | Standard Deviation 0.264 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in Weight-for-Age Z-Score (Double-blind Phase/ Baseline Observation Carried Forward) | 0.14 Z-score | Standard Deviation 0.295 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Double-blind (DB) Baseline as covariate to test the hypothesis of no difference in change in Weight-for-Age Z-Score from DB Baseline to DB Endpoint between Rabeprazole Sodium Total and Placebo.p-value: 0.4495% CI: [-0.047, 0.108]ANCOVA
Secondary
Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward)
The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the subject has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. The Discomfort subscale score will be calculated as the sum of the 3 questions regarding discomfort (Questions, 7, 8, 9) and will range from 0 to 12. For each subscale score, a higher value indicates a worse outcome.
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | 0.0 scores on a scale | Standard Deviation 2.24 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.1 scores on a scale | Standard Deviation 1.88 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.4 scores on a scale | Standard Deviation 1.94 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in Weekly Average I-GERQ-DD Discomfort Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.2 scores on a scale | Standard Deviation 1.9 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Change from Open-label (OL) Baseline to OL Endpoint as covariate to test the hypothesis of no difference in change in weekly average I-GERQ-DD Discomfort Subscale Score from Double-blind (DB) Baseline to DB Endpoint between rabeprazole sodium total and placebo.p-value: 0.47995% CI: [-0.69, 0.325]ANCOVA
Secondary
Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward)
The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the subject has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. The Eating Behavior subscale score will be calculated as the sum of the 3 questions regarding eating behavior (Questions 4, 5, 6) and will range from 0 to 12. For each subscale score, a higher value indicates a worse outcome.
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.1 scores on a scale | Standard Deviation 2.54 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.1 scores on a scale | Standard Deviation 2.19 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.4 scores on a scale | Standard Deviation 2.15 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in Weekly Average I-GERQ-DD Eating Behavior Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.3 scores on a scale | Standard Deviation 2.17 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Change from Open-label (OL) Baseline to OL Endpoint as covariate to test the hypothesis of no difference in change in weekly average I-GERQ-DD Eating Behavior Subscale Score from Double-blind (DB) Baseline to DB Endpoint between rabeprazole sodium total and placebo.p-value: 0.49895% CI: [-0.751, 0.366]ANCOVA
Secondary
Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward)
The Infant Gastroesophageal Reflux Questionnaire-Daily Diary (I-GERQ-DD) is a 9-item daily diary that the primary caregiver will be instructed to complete every evening at the same time interval after the participant has gone to sleep for the night. The I-GERQ-DD contains 3 subscales: the Regurgitation subscale, the Eating Behavior subscale and the Discomfort subscale. The Regurgitation subscale will be calculated as the sum of the 3 questions regarding regurgitation (Questions 1, 2, 3) and will range from 0 to 13. For each subscale score, a higher value indicates a worse outcome.
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Placebo | Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.8 scores on a scale | Standard Deviation 2.57 |
| Double-Blind Rabeprazole Sodium 5 mg | Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.8 scores on a scale | Standard Deviation 2.56 |
| Double-Blind Rabeprazole Sodium 10 mg | Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -1.0 scores on a scale | Standard Deviation 2.38 |
| Double-Blind Rabeprazole Sodium Total | Change From Baseline in Weekly Average I-GERQ-DD Regurgitation Subscale Score (Double-blind Phase/ Last Observation Carried Forward) | -0.9 scores on a scale | Standard Deviation 2.47 |
Comparison: Analysis of Covariance with Treatment as fixed effect, Region and Age as stratification factors and Change from Open-label (OL) Baseline to OL Endpoint as covariate to test the hypothesis of no difference in change in weekly average I-GERQ-DD Regurgitation Subscale Score from Double-blind (DB) Baseline to DB Endpoint between rabeprazole sodium total and placebo.p-value: 0.98495% CI: [-0.619, 0.632]ANCOVA
Secondary
The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period
Time frame: Baseline, Week 8
Population: Intent to Treat population, which consisted of all participants who completed the Open-label period, were randomly assigned to treatment in the Double-blind (DB) period, had taken at least 1 dose of DB study drug, and with evaluable data at each measurement time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Placebo | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.1 number of episodes | Standard Deviation 0.19 |
| Double-Blind Placebo | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.3 number of episodes | Standard Deviation 0.53 |
| Double-Blind Placebo | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 1.2 number of episodes | Standard Deviation 2.52 |
| Double-Blind Placebo | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.05 |
| Double-Blind Placebo | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 0.7 number of episodes | Standard Deviation 1.04 |
| Double-Blind Rabeprazole Sodium 5 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 1.1 number of episodes | Standard Deviation 1.49 |
| Double-Blind Rabeprazole Sodium 5 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.14 |
| Double-Blind Rabeprazole Sodium 5 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.09 |
| Double-Blind Rabeprazole Sodium 5 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 0.7 number of episodes | Standard Deviation 1.08 |
| Double-Blind Rabeprazole Sodium 5 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.2 number of episodes | Standard Deviation 0.43 |
| Double-Blind Rabeprazole Sodium 10 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 1.9 number of episodes | Standard Deviation 4.25 |
| Double-Blind Rabeprazole Sodium 10 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.24 |
| Double-Blind Rabeprazole Sodium 10 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 1.2 number of episodes | Standard Deviation 1.73 |
| Double-Blind Rabeprazole Sodium 10 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.08 |
| Double-Blind Rabeprazole Sodium 10 mg | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.3 number of episodes | Standard Deviation 0.77 |
| Double-Blind Rabeprazole Sodium Total | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.2 number of episodes | Standard Deviation 0.48 |
| Double-Blind Rabeprazole Sodium Total | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 0.8 number of episodes | Standard Deviation 2.15 |
| Double-Blind Rabeprazole Sodium Total | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 0.5 number of episodes | Standard Deviation 1.62 |
| Double-Blind Rabeprazole Sodium Total | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.09 |
| Double-Blind Rabeprazole Sodium Total | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.11 |
| Double-Blind Rabeprazole Sodium 5 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.1 number of episodes | Standard Deviation 0.6 |
| Double-Blind Rabeprazole Sodium 5 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.05 |
| Double-Blind Rabeprazole Sodium 5 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 0.7 number of episodes | Standard Deviation 1.35 |
| Double-Blind Rabeprazole Sodium 5 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 0.4 number of episodes | Standard Deviation 0.75 |
| Double-Blind Rabeprazole Sodium 5 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.14 |
| Double-Blind Rabeprazole Sodium 10 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.23 |
| Double-Blind Rabeprazole Sodium 10 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.04 |
| Double-Blind Rabeprazole Sodium 10 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 0.7 number of episodes | Standard Deviation 1.55 |
| Double-Blind Rabeprazole Sodium 10 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 1.0 number of episodes | Standard Deviation 1.92 |
| Double-Blind Rabeprazole Sodium 10 mg - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.2 number of episodes | Standard Deviation 0.65 |
| Double-Blind Rabeprazole Sodium Total - Baseline | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 1.0 number of episodes | Standard Deviation 1.45 |
| Double-Blind Rabeprazole Sodium Total - Baseline | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.2 number of episodes | Standard Deviation 0.62 |
| Double-Blind Rabeprazole Sodium Total - Baseline | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.2 |
| Double-Blind Rabeprazole Sodium Total - Baseline | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.08 |
| Double-Blind Rabeprazole Sodium Total - Baseline | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 1.5 number of episodes | Standard Deviation 3.18 |
| Double-Blind Rabeprazole Sodium Total - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.04 |
| Double-Blind Rabeprazole Sodium Total - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 fluid oz to 4 fluid oz | 0.0 number of episodes | Standard Deviation 0.19 |
| Double-Blind Rabeprazole Sodium Total - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | Less than 1 tablespoon | 0.9 number of episodes | Standard Deviation 1.66 |
| Double-Blind Rabeprazole Sodium Total - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | 1 to 2 tablespoons | 0.6 number of episodes | Standard Deviation 1.21 |
| Double-Blind Rabeprazole Sodium Total - Week 8 | The Daily Average Number of Episodes Related to Each Volume of Regurgitation During the Double-blind Treatment Period | More than 2 tablespoons to 2 fluid oz | 0.2 number of episodes | Standard Deviation 0.63 |