Clinical trial NCT02246439: BEKINDA (Ondansetron 24 mg Bimodal Release Tablets) for Vomiting Due to Presumed Acute Gastroenteritis or Gastritis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastroenteritis
Gastritis
Keywords: Gastroenteritis
Gastritis
Vomiting
Nausea
Diarrhea
Lead sponsor: RedHill Biopharma Limited
Sponsor class: INDUSTRY
First posted: 2014-09-22
Enrollment: 330
Sex: ALL
Minimum age (years): 12
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population
timeFrame: 24 Hours
Secondary outcomes:
measure: Responders Through 4 Days After First Dose of Study Medication - ITT Population
timeFrame: 4 Days
measure: Number of Participants Who Vomited - ITT Population
timeFrame: 24 Hours
measure: Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population
timeFrame: 24 Hours
measure: Number of Patients Receiving Intravenous Fluids - ITT Population
timeFrame: 24 Hours
measure: Severity of Nausea at Baseline - ITT Population
timeFrame: Day 1 - Baseline through 5 Hours Post Dose
measure: Incidence and Severity of Diarrhea - ITT Population
timeFrame: From 30 Minutes Through 24 Hours after First Dose of Study Medication
measure: Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population
timeFrame: Hours from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last
measure: Time to Resumption of Normal Activities (Work/School/Household) - ITT Population
timeFrame: Hours from first dose of study medication to resumption of normal activities
measure: Number of Patients Requiring Hospitalization - ITT Population
timeFrame: Day 1 of Study - Day 5 of Study
measure: Number of Patients Returning to Emergency Department - ITT Population
timeFrame: Day 1 of Study - Day 5 of Study
Other outcomes:
measure: Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages
timeFrame: 24 Hours
measure: Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population
timeFrame: 24 Hours
Locations:
city: Bakersfield
country: United States
facility: Kern Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Sylmar
country: United States
facility: Olive View- UCLA Medical Center
state: California
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida Jacksonville
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: South Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Wayne State University - Sinai Grace Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University - St. Louis
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: Kings County Hospital
state: New York
city: Brooklyn
country: United States
facility: University Hospital of Brooklyn
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Cohen's Children's Medical Center of NY
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital North
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Mercy
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: CityDoc Urgent Care
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: McAllen
country: United States
facility: McAllen Primary Care
state: Texas
Study officials:
affiliation: Long Island Jewish Hospital (LIJ)
name: Robert Silverman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.