Bimodal Release Oral Ondansetron Shows Promise in Phase 3 Study

Approximately 179 million episodes of acute gastroenteritis occur annually in the United States, resulting in 600,000 hospitalizations and 5000 deaths. Acute gastroenteritis often leads to vomiting which limits the success of fluid replacement for patients with dehydration.

Medications used to treat vomiting in the emergency department include metoclopramide, prochlorperazine, and ondansetron administered intravenously. Intravenous treatment can be costly, uncomfortable for patients, and resource-draining. However, results of a phase 3 clinical trial, published in Jama Network Open, showed positive results for a bimodal release oral ondansetron tablet, finding the drug effective in treating nausea and vomiting.

The bimodal release ondansetron tablet contains 6mg of immediate release ondansetron and 18mg of 24-hour release ondansetron, for a total of 24mg of ondansetron. The study was a double-blind, placebo-controlled, parallel-group, randomized clinical trial evaluating both safety and efficacy for the bimodal release tablet.

The study was conducted among both adolescents and adults. Individuals 12 years and older at 19 different emergency departments and 2 urgent care centers with symptoms of acute gastroenteritis were evaluated for eligibility between December 8, 2014 and February 17, 2017.

Individuals with 2 or more episodes of vomiting in the 4 hours prior to arriving at the center and whose duration of vomiting symptoms was less than 36 hours were eligible for enrollment. Patients were excluded if they were pregnant, had recently undergone an abdominal surgery, had unhealthy alcohol or illicit drug use, had history of bariatric surgical procedures or bowel obstruction, had evidence of severe dehydration, or had serious medical comorbidities.

Patients were evaluated on their nausea symptoms using a 5-point Likert numeric rating scale. The primary outcome was frequency of treatment success at 24 hours after study tablet administration. The study population included all patients who were administered a tablet regardless of whether the tablet was vomited soon after.

A total of 330 patients were randomized, with 321 included in final analysis. The mean age of patients was 29 years, and 195 participants were women. At enrollment, 192 patients were randomized to the bimodal release ondansetron group and 129 patients were randomized to the placebo group.

Adolescents younger than 18 years made up 8% of participants, with 26 patients total. All patients, excluding 5 in the bimodal release group and 2 in the placebo group, had a final diagnosis of acute gastroenteritis. Patients in the bimodal release group reported more severe nausea at the time of randomization than those in the placebo group, as 58 patients and 27 patients reported the highest severity on the Likert scale, respectively.

After modified intention-to-treat analysis, 126 treatment successes were observed in the bimodal release ondansetron group relative to 70 treatment successes in the placebo group. The absolute probability difference for treatment success was 11.4% and the proportion of treatment success was 21% higher for those in the bimodal release ondansetron group compared to those in the placebo group.

Patients whose treatment was successful were given 3 additional tablets on discharge and instructed to take 1 as needed every 24 hours, but most patients did not report taking additional doses, with only 20 of 196 discharged patients taking all 3 additional doses.

After 4 days, treatment remained successful for 114 of the bimodal release ondansetron group compared to 67 patients in the placebo group. Both groups saw 4 patients return to the emergency department for gastrointestinal symptoms within 4 days of initial dosing. Adverse events were not frequent and were similar to the previously known safety profile of ondansetron.

Study authors wrote that “giving oral rather than intravenous therapy in the acute care setting could result in more rapid treatment and disposition using lower acuity treatment areas in which fewer personnel and resources would be needed. Treatment with bimodal release ondansetron presents other outpatient treatment options, including urgent care centers or office and clinic settings, with ED visits reserved for those who fail treatment.”

They noted that the drug appeared to work quickly, and that benefits from the long acting component extended through the 24-hour window after tablet administration. If further study confirms these results, the drug may reduce the burdens like intravenous access and emergency department visits in treatment of acute gastroenteritis.