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

Gastroenteritis Clinical Trial

— GUARD  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02246439
• Other study ID #: RHB-102-01
• Status: Completed
• Phase: Phase 3
• Start date: December 8, 2014
• Est. completion date: February 16, 2017

Study information

• Verified date: January 2019
• Source: RedHill Biopharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: February 16, 2017
• Est. primary completion date: February 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastritis
• Gastroenteritis
• Vomiting

Intervention

Drug:
• RHB-102
RHB-102, Bimodal Release Ondansetron Tablets
• Placebo Oral Tablet
Placebo

Locations

Country	Name	City	State
United States	Kern Medical Center	Bakersfield	California
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Kings County Hospital	Brooklyn	New York
United States	University Hospital of Brooklyn	Brooklyn	New York
United States	CityDoc Urgent Care	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Wayne State University - Sinai Grace Hospital	Detroit	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Baylor College of Medicine	Houston	Texas
United States	University of Florida Jacksonville	Jacksonville	Florida
United States	North Shore University Hospital	Manhasset	New York
United States	McAllen Primary Care	McAllen	Texas
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Cohen's Children's Medical Center of NY	New Hyde Park	New York
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	UPMC Mercy	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	UC Davis	Sacramento	California
United States	Washington University - St. Louis	Saint Louis	Missouri
United States	South Shore Hospital	South Weymouth	Massachusetts
United States	Staten Island University Hospital North	Staten Island	New York
United States	Stony Brook University	Stony Brook	New York
United States	Olive View- UCLA Medical Center	Sylmar	California
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
RedHill Biopharma Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
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	24 Hours
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.	4 Days
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	24 Hours
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.	24 Hours
Secondary	Number of Patients Receiving Intravenous Fluids - ITT Population	Patients receiving parenteral hydration within 24 hours after the first dose of study medication.	24 Hours
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.	Day 1 - Baseline through 5 Hours Post Dose
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.	From 30 Minutes Through 24 Hours after First Dose of Study Medication
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.	Hours from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last
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).	Hours from first dose of study medication to resumption of normal activities
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.	Day 1 of Study - Day 5 of Study
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	Day 1 of Study - Day 5 of Study