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

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)

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 Overview

• Status: Completed
• Conditions: Gastritis; Gastroenteritis
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: RHB-102

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 Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 93311
      • Kern Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis
    • Sylmar, California, United States, 91342
      • Olive View- UCLA Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • South Weymouth, Massachusetts, United States, 02190
      • South Shore Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48235
      • Wayne State University - Sinai Grace Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University - St. Louis
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital
    • Brooklyn, New York, United States, 11203
      • University Hospital of Brooklyn
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New Hyde Park, New York, United States, 11040
      • Cohen's Children's Medical Center of NY
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital North
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15219
      • UPMC Mercy
  • Texas
    • Dallas, Texas, United States, 75209
      • CityDoc Urgent Care
    • Houston, Texas, United States, 77030
      • Baylor College Of Medicine
    • McAllen, Texas, United States, 78503
      • McAllen Primary Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 85 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Oral Tablet; Placebo; Other Names: Placebo
Experimental: RHB-102; RHB-102, Bimodal Release Ondansetron Tablets	Drug: RHB-102; RHB-102, Bimodal Release Ondansetron Tablets

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 Hours
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	24 Hours

Collaborators and Investigators

• Sponsor: RedHill Biopharma Limited
• Investigators: Principal Investigator: Robert Silverman, MD, Long Island Jewish Hospital (LIJ)

Publications and helpful links

General Publications

• Silverman RA, House SL, Meltzer AC, Hahn B, Lovato LM, Avarello J, Miller JB, Kalfus IN, Fathi R, Raday G, Plasse TF, Yan EC. Bimodal Release Ondansetron for Acute Gastroenteritis Among Adolescents and Adults: A Randomized Clinical Trial. JAMA Netw Open. 2019 Nov 1;2(11):e1914988. doi: 10.1001/jamanetworkopen.2019.14988.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2014
• Primary Completion (Actual): February 13, 2017
• Study Completion (Actual): February 16, 2017

Study Registration Dates

• First Submitted: September 16, 2014
• First Submitted That Met QC Criteria: September 18, 2014
• First Posted (Estimate): September 22, 2014

Study Record Updates

• Last Update Posted (Actual): February 20, 2019
• Last Update Submitted That Met QC Criteria: January 28, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Diarrhea; Nausea; Vomiting; Gastroenteritis; Gastritis
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Gastritis; Vomiting; Gastroenteritis
• Other Study ID Numbers: RHB-102-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No