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

Phase 3

Completed

• Conditions: Gastroenteritis; Gastritis
• Interventions: Drug: RHB-102; Drug: Placebo Oral Tablet

• Registration Number: NCT02246439
• Lead Sponsor: RedHill Biopharma Limited

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.

Study Timeline

• Study First Submitted: 2014-09-16
• Study First Submitted QC: 2014-09-18
• Study First Posted: 2014-09-22
• Study Start: 2014-12-08
• Primary Completion: 2017-02-13
• Study Completion: 2017-02-16
• Disposition First Submitted: 2018-02-08
• Disposition First Submitted QC: 2018-02-08
• Disposition First Posted: 2018-02-12
• Results First Submitted: 2018-11-30
• Status Verified: 2019-01
• Results First Submitted QC: 2019-01-28
• Last Update Submitted: 2019-01-28
• Results First Posted: 2019-02-20
• Last Update Posted: 2019-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 330

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RHB-102	RHB-102	RHB-102, Bimodal Release Ondansetron Tablets
Placebo	Placebo Oral Tablet	Placebo

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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).
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

Trial Locations

Locations (26)

Kern Medical Center; 🇺🇸 Bakersfield, California, United States

CityDoc Urgent Care; 🇺🇸 Dallas, Texas, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Washington University - St. Louis; 🇺🇸 Saint Louis, Missouri, United States

George Washington University; 🇺🇸 Washington, District of Columbia, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

UPMC Mercy; 🇺🇸 Pittsburgh, Pennsylvania, United States

UC Davis; 🇺🇸 Sacramento, California, United States

University Hospital of Brooklyn; 🇺🇸 Brooklyn, New York, United States

Wayne State University - Sinai Grace Hospital; 🇺🇸 Detroit, Michigan, United States

Olive View- UCLA Medical Center; 🇺🇸 Sylmar, California, United States

McAllen Primary Care; 🇺🇸 McAllen, Texas, United States

Long Island Jewish Medical Center; 🇺🇸 New Hyde Park, New York, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

University of Florida Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

South Shore Hospital; 🇺🇸 South Weymouth, Massachusetts, United States

Staten Island University Hospital North; 🇺🇸 Staten Island, New York, United States

Kings County Hospital; 🇺🇸 Brooklyn, New York, United States

Stony Brook University; 🇺🇸 Stony Brook, New York, United States

North Shore University Hospital; 🇺🇸 Manhasset, New York, United States

Cohen's Children's Medical Center of NY; 🇺🇸 New Hyde Park, New York, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States