BEKINDA (Ondansetron 24 mg Bimodal Release Tablets) for Vomiting Due to Presumed Acute Gastroenteritis or Gastritis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Placebo-Controlled, Phase 3 Trial of BEKINDA (Ondansetron 24 mg Bimodal Release Tablets) for Vomiting Due to Presumed Acute Gastroenteritis or Gastritis (The GUARD Study)

Conditions
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Gastroenteritis, Gastritis

Intervention / Treatment
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* Drug: RHB-102
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RHB-102<br>RHB-102, Bimodal Release Ondansetron Tablets | Drug: RHB-102<br>* RHB-102, Bimodal Release Ondansetron Tablets<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo Oral Tablet<br>* Placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 24 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 Days | 
| 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 | 24 Hours | 
| Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population | Patients receiving rescue antiemetic therapy within 24 hours after the first dose of study medication. | 24 Hours | 
| Number of Patients Receiving Intravenous Fluids - ITT Population | Patients receiving parenteral hydration within 24 hours after the first dose of study medication. | 24 Hours | 
| 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. | Day 1 - Baseline through 5 Hours Post Dose | 
| 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. | From 30 Minutes Through 24 Hours after First Dose of Study Medication | 
| 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. | Hours from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last | 
| 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). | Hours from first dose of study medication to resumption of normal activities | 
| 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. | Day 1 of Study - Day 5 of Study | 
| 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 | Day 1 of Study - Day 5 of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diarrhea, Gastroenteritis, Gastritis, Vomiting, Nausea