Gastroesophageal Reflux Disease, GERD, Heartburn
Conditions
Keywords
gastroesophageal reflux disease, GERD, heartburn
Brief summary
The objective of this study is to evaluate the efficacy, acceptability, and safety of Axid Oral Solution versus placebo in the treatment of gastroesophageal reflux disease (GERD) in infants age 30 days up to 1 year.
Interventions
DRUGnizatidine (axid)
nizatidine (axid)
DRUGplacebo
placebo
Sponsors
Braintree Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Days to 1 Years
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients age 30 days up to 1 year at Visit 1. * Subjects must have a documented medical diagnosis of gastroesophageal reflux disease (GERD), confirmed by either endoscopy or pH monitoring, or by evaluation of baseline symptoms. * Subjects must be greater than the 3rd percentile of weight and height for their age. * Parents/guardians are competent and willing to provide consent and sign and date the institutional review board (IRB) approved consent form. * Parents/guardians are willing to adhere to study requirements, including applying the conservative GERD management methods. * Conservative GERD management methods have failed to adequately control GERD symptoms by Visit 2. * Parent/guardian and infant live in the same household. * Qualifying caregiver questionnaire score at Visits 1 & 2.
Exclusion criteria
* Any known esophageal disease or disorder, other than reflux esophagitis. * Any active gastroduodenal ulceration, or clinical or endoscopic evidence of active gastrointestinal bleeding. * Any prior esophageal or gastric surgery. * Concurrent serious systemic disorders, including chronic respiratory disease, chronic neurologic disease, chronic renal disease, chronic liver disease. * Subjects with clinically significant abnormal laboratory findings at screening. * Premature infants \< 37 weeks gestation at birth. * Infants with prior neonatal intensive care unit admission for any reason. * Hematemesis or apparent life-threatening events (ALTE). * Concurrent treatment with any chronic medication except by permission of the study sponsor. * Treatment with a histamine 2 receptor antagonist (H2RA), antacid, sucralfate, prostaglandin, or motility agent within 3 days before Visit 1; treatment with a proton pump inhibitor within 7 days before Visit 1. * Requirement or likely requirement for a medical procedure or surgery during the study. * Known hypersensitivity to an H2RA including nizatidine. * Receipt of any investigational agent within the previous 30 days before randomization. * Poor medical or psychiatric risks for therapy with an investigational drug, in the opinion of the investigator. * Any condition in parent/guardian associated with poor subject compliance e.g., substance abuse); inability of parent/guardian to return for scheduled visits with their child.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Success | 8 weeks | The I-GERQ-R contains 12 questions assessing gastroesophageal reflux disease (GERD) frequency and severity. A low I-GERQ-R score (minimum = 0) indicates minimal symptoms and a high I-GERQ-R score (maximum = 42) indicates more frequent and/or severe symptoms. Success is defined as a reduction in I-GERQ-R score of at least 5 points from baseline, provided a subject did not discontinue due to lack of efficacy or adverse event, and had been treated for at least 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | 8 weeks | Subjective investigator assessment of GERD relief - rating categories were BETTER, NO CHANGE, or WORSE from baseline. |
| Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | 8 weeks | Subjective investigator assessment of GERD severity - rating categories were NONE, MILD, MODERATE, or SEVERE. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nizatidine 2.5 mg/kg b.i.d. | 43 |
| Nizatidine 5.0 mg/kg b.i.d. | 50 |
| Conservative Measures Only | 45 |
| Total | 138 |
Baseline characteristics
| Characteristic | Nizatidine 2.5 mg/kg b.i.d. | Nizatidine 5.0 mg/kg b.i.d. | Conservative Measures Only | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 43 Participants | 50 Participants | 45 Participants | 138 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 43 participants | 50 participants | 45 participants | 138 participants |
| Sex: Female, Male Female | 38 Participants | 44 Participants | 38 Participants | 120 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 7 Participants | 18 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 | 27 / 43 | 31 / 50 | 31 / 45 |
| serious Total, serious adverse events | 0 / 43 | 0 / 50 | 1 / 45 |
Outcome results
Primary
Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Success
The I-GERQ-R contains 12 questions assessing gastroesophageal reflux disease (GERD) frequency and severity. A low I-GERQ-R score (minimum = 0) indicates minimal symptoms and a high I-GERQ-R score (maximum = 42) indicates more frequent and/or severe symptoms. Success is defined as a reduction in I-GERQ-R score of at least 5 points from baseline, provided a subject did not discontinue due to lack of efficacy or adverse event, and had been treated for at least 4 weeks.
Time frame: 8 weeks
Population: The analysis population includes all patients that took drug and had any efficacy data reported. 5 patients that were lost to follow up (1 nizatidine 2.5 group, 1 nizatidine 5.0 group, 3 placebo group) were not included because they had no efficacy data and had not reported any adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nizatidine 2.5 mg/kg b.i.d. | Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Success | 27 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Success | 32 participants |
| Conservative Measures Only | Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Success | 31 participants |
p-value: 0.528Cochran-Mantel-Haenszel
p-value: 0.341Cochran-Mantel-Haenszel
Secondary
Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief
Subjective investigator assessment of GERD relief - rating categories were BETTER, NO CHANGE, or WORSE from baseline.
Time frame: 8 weeks
Population: The analysis population includes all patients that took drug and reached the 8 week study timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | No Change | 4 participants |
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | Better | 32 participants |
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | Worse | 5 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | No Change | 2 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | Better | 36 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | Worse | 6 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | Better | 29 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | Worse | 4 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Relief | No Change | 6 participants |
Comparison: Comparison of nizatidine 2.5 group to placebo group. P-value is for overall difference between groups (not comparison of individual categories).p-value: 0.746Chi-squared
Comparison: Comparison of nizatidine 5.0 group to placebo group. P-value is for overall difference between groups (not comparison of individual categories).p-value: 0.262Chi-squared
Secondary
Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity
Subjective investigator assessment of GERD severity - rating categories were NONE, MILD, MODERATE, or SEVERE.
Time frame: 8 weeks
Population: The analysis population includes all patients that took drug and reached the 8 week study timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | None | 3 participants |
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Mild | 25 participants |
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Moderate | 10 participants |
| Nizatidine 2.5 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Severe | 3 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Severe | 2 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | None | 7 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Moderate | 9 participants |
| Nizatidine 5.0 mg/kg b.i.d. | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Mild | 26 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Severe | 1 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Mild | 25 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | Moderate | 7 participants |
| Conservative Measures Only | Investigator Assessment of Gastroesophageal Reflux Disease (GERD) Severity | None | 5 participants |
Comparison: Comparison of nizatidine 2.5 group to placebo group. P-value is for overall difference between groups (not comparison of individual categories).p-value: 0.609Chi-squared
Comparison: Comparison of nizatidine 5.0 group to placebo group. P-value is for overall difference between groups (not comparison of individual categories).p-value: 0.938Chi-squared