Gastritis, Gastroenteritis
Conditions
Keywords
Gastroenteritis, Gastritis, Vomiting, Nausea, Diarrhea
Brief summary
Randomized, Placebo-Controlled, Phase 3 Trial of RHB-102 (BEKINDA) (Ondansetron 24 mg Bimodal Release Tablets) for Acute Gastroenteritis. The study will evaluate the safety and efficacy of RHB-102 (BEKINDA) in treating Acute Gastroenteritis, by comparing it to placebo.
Detailed description
Randomized, Placebo-Controlled, Phase 3 Trial of RHB-102 (BEKINDA) (Ondansetron 24 mg Bimodal Release Tablets) for Acute Gastroenteritis. The study will evaluate the safety and efficacy of RHB-102 (BEKINDA) in treating Acute Gastroenteritis, by comparing it to placebo.
Interventions
DRUGRHB-102
RHB-102, Bimodal Release Ondansetron Tablets
DRUGPlacebo Oral Tablet
Placebo
Sponsors
RedHill Biopharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have vomited at least twice in the 4 hours preceding signing informed consent. A vomiting episode is defined as an episode of forceful expulsion of stomach contents. Retching if a patient has already emptied his or her gastric contents is also considered vomiting episode. A distinct episode is characterized by a clear break in vomiting activity of at least 5 minutes * Emesis must have been nonbloody (streaks of blood presumed due to force of retching are allowed) * All patients (and a parent or guardian for patients \<age 18) must sign informed consent.
Exclusion criteria
* Severe dehydration. Severe dehydration is defined as two or more of the following criteria in the presence of decreased intake and increased output due to vomiting or diarrhea: Absent or severely decreased urine output; weak pulse and/or low blood pressure; parched mucous membranes; lethargy, confusion, delirium or loss of consciousness * Signs and symptoms severe enough to require immediate parenteral hydration and/or parenteral antiemetic medication * Temperature\>39.0 * Likely etiologies for acute vomiting and diarrhea other than acute infectious or toxic gastroenteritis or gastritis. This includes signs of an acute abdomen, which may require surgical intervention * Chemically-induced gastroenteritis, e.g., from alcohol, other drugs of abuse or other irritant chemicals * Use within 24 hours of study entry of specific medication for treatment of nausea and/or vomiting, e.g., 5-HT3 antagonists or phenothiazines, or receipt of any IV fluid for any reason. Nonspecific gastrointestinal remedies, such as antacids, proton pump inhibitors and homeopathic remedies, are permitted. * Congestive heart failure, bradyarrhythmia (baseline pulse\<55/min), known long QT syndrome * Patient who have known QTc prolongation \> 450 msec, noted on prior or screening ECG, or who are taking medication known to cause QT prolongation. Note: for current list of medications known to cause QT prolongation see: https://www.crediblemeds.org/healthcare-providers/drug-list/ Use list showing drugs with known risk TdP. * Known underlying disease which could affect assessment of hydration or modify outcome of treatment, e.g., renal failure, diabetes mellitus, liver disease, alcoholism. Patients with type 2 diet-controlled diabetes mellitus whose baseline blood glucose is \<200 may be entered into the study * Abdominal surgery within the past 3 months * History of bariatric surgery or bowel obstruction at any time * Hypersensitivity or other known intolerance to ondansetron or other 5-HT3 antagonists * Patient has taken apomorphine within 24 hours of screening * Patient has previously participated in this study * Patient has participated in another interventional clinical trial, for any indication, in the past 30 days * For women of childbearing potential: documented or possible pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | 24 Hours | Number of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responders Through 4 Days After First Dose of Study Medication - ITT Population | 4 Days | Treatment success, as defined in the primary outcome, through 4 days following first dose of study medication. |
| Number of Participants Who Vomited - ITT Population | 24 Hours | Analysis of vomiting from 30 minutes after first administration of study medication until 24 hours post first dose |
| Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population | 24 Hours | Patients receiving rescue antiemetic therapy within 24 hours after the first dose of study medication. |
| Number of Patients Receiving Intravenous Fluids - ITT Population | 24 Hours | Patients receiving parenteral hydration within 24 hours after the first dose of study medication. |
| Severity of Nausea at Baseline - ITT Population | Day 1 - Baseline through 5 Hours Post Dose | Severity of nausea was assessed using a 5-point Likert scale: 0=no nausea; 1=mild nausea; 2=moderate nausea; 3=severe nausea; 4=nausea as bad as can be. |
| Number of Patients Requiring Hospitalization - ITT Population | Day 1 of Study - Day 5 of Study | Number of patients requiring hospitalization. 4 patients in the RHB-102 treatment group and 1 patient in the placebo treatment group were hospitalized due to lack of efficacy. The remaining patients hospitalized were admitted for reasons other than gastroenteritis. |
| Number of Patients Returning to Emergency Department - ITT Population | Day 1 of Study - Day 5 of Study | Proportion of patients returning to emergency department for gastrointestinal symptoms within 4 days of initial discharge |
| Incidence and Severity of Diarrhea - ITT Population | From 30 Minutes Through 24 Hours after First Dose of Study Medication | Severity of diarrhea for patients having bowel movements was assessed using the Bristol Stool Scale (BSS), a Likert scale rating bowel movements from 1=separate hard lumps, like nuts, to 7=watery, no solid pieces; entirely liquid. The BSS was added to the emergency room day and follow-up diaries beginning with protocol amendment 3. |
| Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | Hours from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last | Time from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last, and when clinically appropriate. |
| Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | Hours from first dose of study medication to resumption of normal activities | Time from first dose of study medication to resumption of normal activities (work/school/household). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | 24 Hours | Proportion of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose |
| Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | 24 Hours | Proportion of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose |
Countries
United States
Participant flow
Recruitment details
First patient randomized: 08 December 2014 Last patient completed: 17 February 2017 This study was conducted in Emergency Departments (EDs) and urgent care centers across the United States. Only 2 sites were urgent care centers; the rest were EDs.
Participants by arm
| Arm | Count |
|---|---|
| RHB-102 1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days. | 192 |
| Placebo 1 tablet of matching placebo, once daily for up to 4 days. | 129 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 7 | 5 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Unkonwn | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | RHB-102 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 29.5 years STANDARD_DEVIATION 11.92 | 28.4 years STANDARD_DEVIATION 9.69 | 29.0 years STANDARD_DEVIATION 11.08 |
| Age, Customized <18 years | 15 Participants | 11 Participants | 26 Participants |
| Age, Customized 18 years or older | 177 Participants | 118 Participants | 295 Participants |
| Nausea Mild nausea | 24 Participants | 15 Participants | 39 Participants |
| Nausea Moderate nausea | 38 Participants | 40 Participants | 78 Participants |
| Nausea Nausea as bad as could be | 58 Participants | 27 Participants | 85 Participants |
| Nausea No nausea | 2 Participants | 3 Participants | 5 Participants |
| Nausea Severe nausea | 70 Participants | 44 Participants | 114 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 11 Participants | 24 Participants |
| Race/Ethnicity, Customized Black or African American | 80 Participants | 56 Participants | 136 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 49 Participants | 28 Participants | 77 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 140 Participants | 99 Participants | 239 Participants |
| Race/Ethnicity, Customized Other | 21 Participants | 14 Participants | 35 Participants |
| Race/Ethnicity, Customized White | 77 Participants | 46 Participants | 123 Participants |
| Sex: Female, Male Female | 122 Participants | 73 Participants | 195 Participants |
| Sex: Female, Male Male | 70 Participants | 56 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 193 | 0 / 128 |
| other Total, other adverse events | 44 / 193 | 19 / 128 |
| serious Total, serious adverse events | 5 / 193 | 2 / 128 |
Outcome results
Primary
Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population
Number of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose
Time frame: 24 Hours
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | All ages | 126 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | <18 years of age | 12 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | 18 years of age or older | 114 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | All ages | 70 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | <18 years of age | 5 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population | 18 years of age or older | 65 Participants |
Comparison: The odds ratio and p-value were from a Cochran-Mantel-Haenszel test. For the 'All ages' category, the odds ratio and p-value were stratified by age.p-value: 0.040695% CI: [1.0194, 2.5368]Cochran-Mantel-Haenszel
p-value: 0.072995% CI: [0.847, 27.2024]Cochran-Mantel-Haenszel
p-value: 0.108995% CI: [0.917, 2.3741]Cochran-Mantel-Haenszel
Secondary
Incidence and Severity of Diarrhea - ITT Population
Severity of diarrhea for patients having bowel movements was assessed using the Bristol Stool Scale (BSS), a Likert scale rating bowel movements from 1=separate hard lumps, like nuts, to 7=watery, no solid pieces; entirely liquid. The BSS was added to the emergency room day and follow-up diaries beginning with protocol amendment 3.
Time frame: From 30 Minutes Through 24 Hours after First Dose of Study Medication
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | No bowel movement | 48 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 1 | 2 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 2 | 1 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 3 | 6 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 4 | 10 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 5 | 6 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 6 | 3 Participants |
| RHB-102 | Incidence and Severity of Diarrhea - ITT Population | BSS 7 | 19 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 7 | 13 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | No bowel movement | 29 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 4 | 5 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 1 | 2 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 6 | 7 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 2 | 2 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 5 | 2 Participants |
| Placebo Oral Tablet | Incidence and Severity of Diarrhea - ITT Population | BSS 3 | 2 Participants |
p-value: 0.589Wilcoxon (Mann-Whitney)
Secondary
Number of Participants Who Vomited - ITT Population
Analysis of vomiting from 30 minutes after first administration of study medication until 24 hours post first dose
Time frame: 24 Hours
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-102 | Number of Participants Who Vomited - ITT Population | Yes | 38 Participants |
| RHB-102 | Number of Participants Who Vomited - ITT Population | No | 131 Participants |
| RHB-102 | Number of Participants Who Vomited - ITT Population | Missing | 23 Participants |
| Placebo Oral Tablet | Number of Participants Who Vomited - ITT Population | Yes | 33 Participants |
| Placebo Oral Tablet | Number of Participants Who Vomited - ITT Population | No | 71 Participants |
| Placebo Oral Tablet | Number of Participants Who Vomited - ITT Population | Missing | 25 Participants |
p-value: 0.016695% CI: [1.1058, 2.776]Cochran-Mantel-Haenszel
Secondary
Number of Patients Receiving Intravenous Fluids - ITT Population
Patients receiving parenteral hydration within 24 hours after the first dose of study medication.
Time frame: 24 Hours
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Number of Patients Receiving Intravenous Fluids - ITT Population | 34 Participants |
| Placebo Oral Tablet | Number of Patients Receiving Intravenous Fluids - ITT Population | 32 Participants |
p-value: 0.123595% CI: [0.3826, 1.1268]Cochran-Mantel-Haenszel
Secondary
Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population
Patients receiving rescue antiemetic therapy within 24 hours after the first dose of study medication.
Time frame: 24 Hours
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population | 48 Participants |
| Placebo Oral Tablet | Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population | 43 Participants |
p-value: 0.104995% CI: [0.4093, 1.0892]Cochran-Mantel-Haenszel
Secondary
Number of Patients Requiring Hospitalization - ITT Population
Number of patients requiring hospitalization. 4 patients in the RHB-102 treatment group and 1 patient in the placebo treatment group were hospitalized due to lack of efficacy. The remaining patients hospitalized were admitted for reasons other than gastroenteritis.
Time frame: Day 1 of Study - Day 5 of Study
Population: The number of treated patients requiring hospitalization was low in this study (14 patients). In the RHB-102 group, 11 patients (5.7%) were hospitalized, including one who returned to the ED for gastrointestinal symptoms 2 days after initial treatment. In the placebo treatment group, 3 patients (2.3%) were hospitalized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Number of Patients Requiring Hospitalization - ITT Population | 11 Participants |
| Placebo Oral Tablet | Number of Patients Requiring Hospitalization - ITT Population | 3 Participants |
p-value: 0.200595% CI: [0.6221, 8.5129]Cochran-Mantel-Haenszel
Secondary
Number of Patients Returning to Emergency Department - ITT Population
Proportion of patients returning to emergency department for gastrointestinal symptoms within 4 days of initial discharge
Time frame: Day 1 of Study - Day 5 of Study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Number of Patients Returning to Emergency Department - ITT Population | 4 Participants |
| Placebo Oral Tablet | Number of Patients Returning to Emergency Department - ITT Population | 4 Participants |
p-value: 0.57295% CI: [0.1638, 2.7191]Cochran-Mantel-Haenszel
Secondary
Responders Through 4 Days After First Dose of Study Medication - ITT Population
Treatment success, as defined in the primary outcome, through 4 days following first dose of study medication.
Time frame: 4 Days
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Responders Through 4 Days After First Dose of Study Medication - ITT Population | 114 Participants |
| Placebo Oral Tablet | Responders Through 4 Days After First Dose of Study Medication - ITT Population | 67 Participants |
p-value: 0.184395% CI: [0.8647, 2.1216]Cochran-Mantel-Haenszel
Secondary
Severity of Nausea at Baseline - ITT Population
Severity of nausea was assessed using a 5-point Likert scale: 0=no nausea; 1=mild nausea; 2=moderate nausea; 3=severe nausea; 4=nausea as bad as can be.
Time frame: Day 1 - Baseline through 5 Hours Post Dose
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RHB-102 | Severity of Nausea at Baseline - ITT Population | Baseline | 2.8 score on a scale | Standard Deviation 1.03 |
| RHB-102 | Severity of Nausea at Baseline - ITT Population | Hour 1 Post Dose | 1.1 score on a scale | Standard Deviation 1.1 |
| RHB-102 | Severity of Nausea at Baseline - ITT Population | Hour 2 Post Dose | 0.8 score on a scale | Standard Deviation 0.97 |
| RHB-102 | Severity of Nausea at Baseline - ITT Population | Hour 3 Post Dose | 0.5 score on a scale | Standard Deviation 0.85 |
| RHB-102 | Severity of Nausea at Baseline - ITT Population | Hour 4 Post Dose | 0.4 score on a scale | Standard Deviation 0.75 |
| RHB-102 | Severity of Nausea at Baseline - ITT Population | Hour 5 Post Dose | 0.1 score on a scale | Standard Deviation 0.42 |
| Placebo Oral Tablet | Severity of Nausea at Baseline - ITT Population | Hour 4 Post Dose | 0.6 score on a scale | Standard Deviation 1.04 |
| Placebo Oral Tablet | Severity of Nausea at Baseline - ITT Population | Baseline | 2.6 score on a scale | Standard Deviation 1.02 |
| Placebo Oral Tablet | Severity of Nausea at Baseline - ITT Population | Hour 3 Post Dose | 0.8 score on a scale | Standard Deviation 1.05 |
| Placebo Oral Tablet | Severity of Nausea at Baseline - ITT Population | Hour 1 Post Dose | 1.3 score on a scale | Standard Deviation 1.16 |
| Placebo Oral Tablet | Severity of Nausea at Baseline - ITT Population | Hour 5 Post Dose | 0.2 score on a scale | Standard Deviation 0.49 |
| Placebo Oral Tablet | Severity of Nausea at Baseline - ITT Population | Hour 2 Post Dose | 0.9 score on a scale | Standard Deviation 1.07 |
Secondary
Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population
Time from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last, and when clinically appropriate.
Time frame: Hours from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last
Population: Patients were required to stay in the ED for at least 2 hours (first 172 patients) and subsequently, when post-treatment ECGs were introduced, for 4 hours. Since not all patients had prolonged ED stays, a difference in time until patients were clinically eligible for discharge may have been masked.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RHB-102 | Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | All ages | 4.3 Hours |
| RHB-102 | Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | < 18 years of age | 4.3 Hours |
| RHB-102 | Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | 18 years of age or older | 4.3 Hours |
| Placebo Oral Tablet | Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | All ages | 4.3 Hours |
| Placebo Oral Tablet | Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | < 18 years of age | 4.8 Hours |
| Placebo Oral Tablet | Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population | 18 years of age or older | 4.2 Hours |
p-value: 0.848795% CI: [0.7803, 1.2264]Cox proportioanl hazards method
p-value: 0.347995% CI: [0.6549, 3.325]Cox proportional hazards method
p-value: 0.633295% CI: [0.7469, 1.1943]Cox proportional hazards method
Secondary
Time to Resumption of Normal Activities (Work/School/Household) - ITT Population
Time from first dose of study medication to resumption of normal activities (work/school/household).
Time frame: Hours from first dose of study medication to resumption of normal activities
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RHB-102 | Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | All ages | 3 Hours |
| RHB-102 | Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | < 18 years of age | 2 Hours |
| RHB-102 | Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | 18 years of age or older | 3 Hours |
| Placebo Oral Tablet | Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | All ages | 3 Hours |
| Placebo Oral Tablet | Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | < 18 years of age | 4 Hours |
| Placebo Oral Tablet | Time to Resumption of Normal Activities (Work/School/Household) - ITT Population | 18 years of age or older | 3 Hours |
p-value: 0.828995% CI: [0.8036, 1.3138]Cox proportional hazards method
p-value: 0.324195% CI: [0.6388, 3.8802]Cox proportional hazards method
p-value: 0.951195% CI: [0.7688, 1.2801]Cox proportional hazards method
Post Hoc
Primary Endpoint Subgroup Analysis - PP Population
Examination of treatment success rates by age (\<18 and ≥18 years).
Time frame: 24 Hours
Population: The Per Protocol (PP) Population contained all patients who met all inclusion/exclusion criteria, received a second dose of medication if they vomited within 15 minutes of receiving first dose, and did not have a primary diagnosis upon discharge from the ED (or, if admitted, discharge from the hospital) other than acute gastroenteritis/gastritis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-102 | Primary Endpoint Subgroup Analysis - PP Population | < 18 years of age | 11 Participants |
| RHB-102 | Primary Endpoint Subgroup Analysis - PP Population | 18 years of age or older | 112 Participants |
| Placebo Oral Tablet | Primary Endpoint Subgroup Analysis - PP Population | < 18 years of age | 5 Participants |
| Placebo Oral Tablet | Primary Endpoint Subgroup Analysis - PP Population | 18 years of age or older | 62 Participants |
p-value: 0.092495% CI: [0.7699, 25.145]Cochran-Mantel-Haenszel
p-value: 0.030395% CI: [1.0527, 2.8615]Cochran-Mantel-Haenszel
Other Pre-specified
Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages
Proportion of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose
Time frame: 24 Hours
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | No nausea or mild nausea | 22 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | Moderate nausea | 26 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | Severe nausea | 47 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | Nausea as bad as it could have been | 31 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | Nausea as bad as it could have been | 11 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | No nausea or mild nausea | 13 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | Severe nausea | 22 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages | Moderate nausea | 24 Participants |
p-value: 0.318695% CI: [0.477, 9.7735]Cochran-Mantel-Haenszel
p-value: 0.347395% CI: [0.6096, 4.0696]Cochran-Mantel-Haenszel
p-value: 0.063395% CI: [0.9614, 4.5747]Cochran-Mantel-Haenszel
p-value: 0.279795% CI: [0.6649, 4.0437]Cochran-Mantel-Haenszel
Post Hoc
Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population (Logistic Regression Adjusted by Baseline Nausea Severity)
Number of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose (analyzed using logistic regression with treatment as a factor and baseline nausea severity as a continuous variable)
Time frame: 24 Hours
Population: The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication. The primary efficacy analysis was conducted using the ITT Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population (Logistic Regression Adjusted by Baseline Nausea Severity) | 126 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population (Logistic Regression Adjusted by Baseline Nausea Severity) | 70 Participants |
p-value: 0.015295% CI: [1.1188, 2.871]Regression, Logistic
Other Pre-specified
Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population
Proportion of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose
Time frame: 24 Hours
Population: The Per Protocol Population contained all patients who met all inclusion/exclusion criteria, received a second dose of study medication if they vomited within 15 minutes of receiving the first dose, \& did not have a primary diagnosis upon discharge from ED (or, if admitted, discharge from the hospital) other than acute gastroenteritis/gastritis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | <18 years of age | 11 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | All ages | 123 Participants |
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | 18 years of age or older | 112 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | All ages | 67 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | <18 years of age | 5 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population | 18 years of age or older | 62 Participants |
p-value: 0.093495% CI: [0.7699, 25.145]Cochran-Mantel-Haenszel
p-value: 0.030395% CI: [1.0527, 2.8615]Cochran-Mantel-Haenszel
p-value: 0.010395% CI: [1.1572, 3.0131]Cochran-Mantel-Haenszel
Post Hoc
Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population (Logistic Regression Adjusted by Baseline Nausea Severity)
Number of patients without further vomiting, without rescue medication, and who were not given intravenous hydration from 30 minutes post first dose until 24 hours post dose (analyzed using logistic regression with treatment as a factor and baseline nausea severity as a continuous variable)
Time frame: 24 Hours
Population: The Per Protocol Population contained all patients who met all inclusion/exclusion criteria, received a second dose of medication if they vomited within 15 minutes of receiving the first dose, and did not have a primary diagnosis upon discharge from the ED (or, if admitted, discharge from the hospital) other than acute gastroenteritis/gastritis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHB-102 | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population (Logistic Regression Adjusted by Baseline Nausea Severity) | 123 Participants |
| Placebo Oral Tablet | Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population (Logistic Regression Adjusted by Baseline Nausea Severity) | 67 Participants |
p-value: 0.003795% CI: [1.2676, 3.4095]Regression, Logistic