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Trial record 10 of 12 for:    RedHill Biopharma

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02246439
Recruitment Status : Completed
First Posted : September 22, 2014
Results First Posted : February 20, 2019
Last Update Posted : February 20, 2019
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Gastroenteritis
Gastritis
Interventions Drug: RHB-102
Drug: Placebo Oral Tablet
Enrollment 330
Recruitment Details

First patient randomized: 08 December 2014 Last patient completed: 17 February 2017

This study was conducted in Emergency Departments (EDs) and urgent care centers across the United States. Only 2 sites were urgent care centers; the rest were EDs.

Pre-assignment Details  
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description 1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days. 1 tablet of matching placebo, once daily for up to 4 days.
Period Title: Overall Study
Started [1] 192 [2] 129 [3]
Randomized 198 132
Completed 180 118
Not Completed 12 11
Reason Not Completed
Adverse Event             3             0
Lost to Follow-up             7             5
Protocol Violation             0             2
Physician Decision             0             1
Unkonwn             1             3
Withdrawal by Subject             1             0
[1]
ITT Population (treated)
[2]
6 participants that enrolled in the study did not receive allocated intervention.
[3]
3 participants that enrolled in the study did not receive allocated intervention.
Arm/Group Title RHB-102 Placebo Total
Hide Arm/Group Description 1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days. 1 tablet of matching placebo, once daily for up to 4 days. Total of all reporting groups
Overall Number of Baseline Participants 192 129 321
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 192 participants 129 participants 321 participants
29.5  (11.92) 28.4  (9.69) 29.0  (11.08)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 129 participants 321 participants
<18 years
15
   7.8%
11
   8.5%
26
   8.1%
18 years or older
177
  92.2%
118
  91.5%
295
  91.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 129 participants 321 participants
Female
122
  63.5%
73
  56.6%
195
  60.7%
Male
70
  36.5%
56
  43.4%
126
  39.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 129 participants 321 participants
American Indian or Alaskan Native
0
   0.0%
1
   0.8%
1
   0.3%
Asian
13
   6.8%
11
   8.5%
24
   7.5%
Black or African American
80
  41.7%
56
  43.4%
136
  42.4%
Native Hawaiian or Other Pacific Islander
1
   0.5%
1
   0.8%
2
   0.6%
White
77
  40.1%
46
  35.7%
123
  38.3%
Other
21
  10.9%
14
  10.9%
35
  10.9%
Hispanic/Latino
49
  25.5%
28
  21.7%
77
  24.0%
Not Hispanic/Latino
140
  72.9%
99
  76.7%
239
  74.5%
Nausea  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 192 participants 129 participants 321 participants
No nausea
2
   1.0%
3
   2.3%
5
   1.6%
Mild nausea
24
  12.5%
15
  11.6%
39
  12.1%
Moderate nausea
38
  19.8%
40
  31.0%
78
  24.3%
Severe nausea
70
  36.5%
44
  34.1%
114
  35.5%
Nausea as bad as could be
58
  30.2%
27
  20.9%
85
  26.5%
1.Primary Outcome
Title Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population
Hide Description 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
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
All ages Number Analyzed 192 participants 129 participants
126
  65.6%
70
  54.3%
<18 years of age Number Analyzed 15 participants 11 participants
12
  80.0%
5
  45.5%
18 years of age or older Number Analyzed 177 participants 118 participants
114
  64.4%
65
  55.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments The odds ratio and p-value were from a Cochran-Mantel-Haenszel test. For the ‘All ages’ category, the odds ratio and p-value were stratified by age.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0406
Comments This P-Value is for the "All ages" group
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.6081
Confidence Interval (2-Sided) 95%
1.0194 to 2.5368
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0729
Comments This P-Value is for the "<18 years of age" group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.800
Confidence Interval (2-Sided) 95%
0.8470 to 27.2024
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1089
Comments This P-Value is for the "18 years of age and older" group
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4755
Confidence Interval (2-Sided) 95%
0.9170 to 2.3741
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Responders Through 4 Days After First Dose of Study Medication - ITT Population
Hide Description Treatment success, as defined in the primary outcome, through 4 days following first dose of study medication.
Time Frame 4 Days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
114
  59.4%
67
  51.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1843
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.3545
Confidence Interval (2-Sided) 95%
0.8647 to 2.1216
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Who Vomited - ITT Population
Hide Description Analysis of vomiting from 30 minutes after first administration of study medication until 24 hours post first dose
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
38
  19.8%
33
  25.6%
No
131
  68.2%
71
  55.0%
Missing
23
  12.0%
25
  19.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0166
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.7520
Confidence Interval (2-Sided) 95%
1.1058 to 2.7760
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Patients Receiving Rescue Antiemetic Therapy - ITT Population
Hide Description Patients receiving rescue antiemetic therapy within 24 hours after the first dose of study medication.
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
48
  25.0%
43
  33.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1049
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6677
Confidence Interval (2-Sided) 95%
0.4093 to 1.0892
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Patients Receiving Intravenous Fluids - ITT Population
Hide Description Patients receiving parenteral hydration within 24 hours after the first dose of study medication.
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
34
  17.7%
32
  24.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1235
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6566
Confidence Interval (2-Sided) 95%
0.3826 to 1.1268
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Severity of Nausea at Baseline - ITT Population
Hide Description 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.
Time Frame Day 1 - Baseline through 5 Hours Post Dose
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 2.8  (1.03) 2.6  (1.02)
Hour 1 Post Dose 1.1  (1.10) 1.3  (1.16)
Hour 2 Post Dose 0.8  (0.97) 0.9  (1.07)
Hour 3 Post Dose 0.5  (0.85) 0.8  (1.05)
Hour 4 Post Dose 0.4  (0.75) 0.6  (1.04)
Hour 5 Post Dose 0.1  (0.42) 0.2  (0.49)
7.Secondary Outcome
Title Incidence and Severity of Diarrhea - ITT Population
Hide Description 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 Frame From 30 Minutes Through 24 Hours after First Dose of Study Medication
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 95 62
Measure Type: Count of Participants
Unit of Measure: Participants
No bowel movement
48
  50.5%
29
  46.8%
BSS 1
2
   2.1%
2
   3.2%
BSS 2
1
   1.1%
2
   3.2%
BSS 3
6
   6.3%
2
   3.2%
BSS 4
10
  10.5%
5
   8.1%
BSS 5
6
   6.3%
2
   3.2%
BSS 6
3
   3.2%
7
  11.3%
BSS 7
19
  20.0%
13
  21.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5890
Comments This P-Value is for the BSS=7 group.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Time to Discharge From Emergency Department (ED), Extended Observation Unit, or Hospital - ITT Population
Hide Description Time from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last, and when clinically appropriate.
Time Frame Hours from first dose of study medication to discharge from ED, extended observation unit or hospital, whichever comes last
Hide Outcome Measure Data
Hide Analysis Population Description
Patients were required to stay in the ED for at least 2 hours (first 172 patients) and subsequently, when post-treatment ECGs were introduced, for 4 hours. Since not all patients had prolonged ED stays, a difference in time until patients were clinically eligible for discharge may have been masked.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Median (95% Confidence Interval)
Unit of Measure: Hours
All ages Number Analyzed 192 participants 129 participants
4.3
(4.1 to 4.5)
4.3
(4.0 to 4.6)
< 18 years of age Number Analyzed 15 participants 11 participants
4.3
(2.9 to 4.7)
4.8
(3.0 to 6.8)
18 years of age or older Number Analyzed 177 participants 118 participants
4.3
(4.1 to 4.5)
4.2
(4.0 to 4.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8487
Comments This P-Value is for the "All ages" group.
Method Cox proportioanl hazards method
Comments Stratified by age.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9782
Confidence Interval (2-Sided) 95%
0.7803 to 1.2264
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3479
Comments This P-Value is for the "<18 years of age" group.
Method Cox proportional hazards method
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.4756
Confidence Interval (2-Sided) 95%
0.6549 to 3.3250
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6332
Comments This P-Value is for the "18 years of age of older" group.
Method Cox proportional hazards method
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9445
Confidence Interval (2-Sided) 95%
0.7469 to 1.1943
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to Resumption of Normal Activities (Work/School/Household) - ITT Population
Hide Description Time from first dose of study medication to resumption of normal activities (work/school/household).
Time Frame Hours from first dose of study medication to resumption of normal activities
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Median (95% Confidence Interval)
Unit of Measure: Hours
All ages Number Analyzed 192 participants 129 participants
3
(3 to 4)
3
(3 to 4)
< 18 years of age Number Analyzed 15 participants 11 participants
2
(1 to 4)
4
(2 to 5)
18 years of age or older Number Analyzed 177 participants 118 participants
3
(3 to 4)
3
(NA to NA)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8289
Comments This P-Value was for the "All ages" group.
Method Cox proportional hazards method
Comments Stratified by age.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.0275
Confidence Interval (2-Sided) 95%
0.8036 to 1.3138
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3241
Comments This P-Value is for the "<18 years of age" group.
Method Cox proportional hazards method
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.5744
Confidence Interval (2-Sided) 95%
0.6388 to 3.8802
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9511
Comments This P-Value is for the "18 years of age or older" group.
Method Cox proportional hazards method
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9920
Confidence Interval (2-Sided) 95%
0.7688 to 1.2801
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Patients Requiring Hospitalization - ITT Population
Hide Description 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.
Time Frame Day 1 of Study - Day 5 of Study
Hide Outcome Measure Data
Hide Analysis Population Description
The number of treated patients requiring hospitalization was low in this study (14 patients). In the RHB-102 group, 11 patients (5.7%) were hospitalized, including one who returned to the ED for gastrointestinal symptoms 2 days after initial treatment. In the placebo treatment group, 3 patients (2.3%) were hospitalized.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
11
   5.7%
3
   2.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2005
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.3012
Confidence Interval (2-Sided) 95%
0.6221 to 8.5129
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Patients Returning to Emergency Department - ITT Population
Hide Description Proportion of patients returning to emergency department for gastrointestinal symptoms within 4 days of initial discharge
Time Frame Day 1 of Study - Day 5 of Study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
4
   2.1%
4
   3.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5720
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6674
Confidence Interval (2-Sided) 95%
0.1638 to 2.7191
Estimation Comments [Not Specified]
12.Other Pre-specified Outcome
Title Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication by Baseline Nausea Severity - ITT Population, All Ages
Hide Description 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
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
No nausea or mild nausea Number Analyzed 26 participants 18 participants
22
  84.6%
13
  72.2%
Moderate nausea Number Analyzed 38 participants 40 participants
26
  68.4%
24
  60.0%
Severe nausea Number Analyzed 70 participants 44 participants
47
  67.1%
22
  50.0%
Nausea as bad as it could have been Number Analyzed 58 participants 27 participants
31
  53.4%
11
  40.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3186
Comments This P-Value is for the "No nausea or mild nausea" group.
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.1591
Confidence Interval (2-Sided) 95%
0.4770 to 9.7735
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3473
Comments This P-Value is for the "Moderate nausea" group.
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.5750
Confidence Interval (2-Sided) 95%
0.6096 to 4.0696
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0633
Comments This P-Value is for the "Severe nausea" group.
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.0971
Confidence Interval (2-Sided) 95%
0.9614 to 4.5747
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2797
Comments This P-Value is for the "Nausea as bad as it could have been" group.
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.6397
Confidence Interval (2-Sided) 95%
0.6649 to 4.0437
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population
Hide Description 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
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Population contained all patients who met all inclusion/exclusion criteria, received a second dose of study medication if they vomited within 15 minutes of receiving the first dose, & did not have a primary diagnosis upon discharge from ED (or, if admitted, discharge from the hospital) other than acute gastroenteritis/gastritis.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 177 122
Measure Type: Count of Participants
Unit of Measure: Participants
All ages Number Analyzed 177 participants 122 participants
123
  69.5%
67
  54.9%
<18 years of age Number Analyzed 14 participants 11 participants
11
  78.6%
5
  45.5%
18 years of age or older Number Analyzed 163 participants 111 participants
112
  68.7%
62
  55.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0103
Comments This P-Value is for the "All ages" group.
Method Cochran-Mantel-Haenszel
Comments Stratified by age.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.8673
Confidence Interval (2-Sided) 95%
1.1572 to 3.0131
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0934
Comments This P-Value is for the "<18 years of age" group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.4000
Confidence Interval (2-Sided) 95%
0.7699 to 25.1450
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0303
Comments This P-Value is for the "18 years of age or older" group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.7356
Confidence Interval (2-Sided) 95%
1.0527 to 2.8615
Estimation Comments [Not Specified]
14.Post-Hoc Outcome
Title Primary Endpoint Subgroup Analysis - PP Population
Hide Description Examination of treatment success rates by age (<18 and ≥18 years).
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol (PP) Population contained all patients who met all inclusion/exclusion criteria, received a second dose of medication if they vomited within 15 minutes of receiving first dose, and did not have a primary diagnosis upon discharge from the ED (or, if admitted, discharge from the hospital) other than acute gastroenteritis/gastritis.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 177 122
Measure Type: Count of Participants
Unit of Measure: Participants
< 18 years of age Number Analyzed 14 participants 11 participants
11
  78.6%
5
  45.5%
18 years of age or older Number Analyzed 163 participants 111 participants
112
  68.7%
62
  55.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0924
Comments This P-Value is for the "<18 years of age" group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.4000
Confidence Interval (2-Sided) 95%
0.7699 to 25.1450
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0303
Comments This P-Value is for the "18 years of age or older" group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.7356
Confidence Interval (2-Sided) 95%
1.0527 to 2.8615
Estimation Comments [Not Specified]
15.Post-Hoc Outcome
Title Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - ITT Population (Logistic Regression Adjusted by Baseline Nausea Severity)
Hide Description 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 (analyzed using logistic regression with treatment as a factor and baseline nausea severity as a continuous variable)
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population consisted of all patients who received any study medication, even if they vomited shortly after administration or were unable to swallow the medication. The primary efficacy analysis was conducted using the ITT Population.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 192 129
Measure Type: Count of Participants
Unit of Measure: Participants
126
  65.6%
70
  54.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0152
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.7922
Confidence Interval (2-Sided) 95%
1.1188 to 2.8710
Estimation Comments [Not Specified]
16.Post-Hoc Outcome
Title Treatment Success From 30 Minutes Through 24 Hours After First Dose of Study Medication - PP Population (Logistic Regression Adjusted by Baseline Nausea Severity)
Hide Description 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 (analyzed using logistic regression with treatment as a factor and baseline nausea severity as a continuous variable)
Time Frame 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Population contained all patients who met all inclusion/exclusion criteria, received a second dose of medication if they vomited within 15 minutes of receiving the first dose, and did not have a primary diagnosis upon discharge from the ED (or, if admitted, discharge from the hospital) other than acute gastroenteritis/gastritis.
Arm/Group Title RHB-102 Placebo Oral Tablet
Hide Arm/Group Description:
1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days.
1 tablet of matching placebo, once daily for up to 4 days.
Overall Number of Participants Analyzed 177 122
Measure Type: Count of Participants
Unit of Measure: Participants
123
  69.5%
67
  54.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo Oral Tablet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.0789
Confidence Interval (2-Sided) 95%
1.2676 to 3.4095
Estimation Comments [Not Specified]
Time Frame 2 years, 3 months
Adverse Event Reporting Description A treatment-emergent adverse event (TEAE) is an adverse event occurring from the start of study medication.
 
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description 1 tablet containing 6 mg immediate release and 18 mg sustained release ondansetron, once daily for up to 4 days. 1 tablet of matching placebo, once daily for up to 4 days.
All-Cause Mortality
RHB-102 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/193 (0.00%)   0/128 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
RHB-102 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   5/193 (2.59%)   2/128 (1.56%) 
Blood and lymphatic system disorders     
Sideroblastic Anaemia  1  1/193 (0.52%)  0/128 (0.00%) 
Gastrointestinal disorders     
Small Intestinal Obstruction  1  1/193 (0.52%)  1/128 (0.78%) 
Diverticulitis Intestinal Haemorrhagic  1  1/193 (0.52%)  0/128 (0.00%) 
Hepatobiliary disorders     
Bile Duct Stone  1  1/193 (0.52%)  0/128 (0.00%) 
Cholecystitis  1  1/193 (0.52%)  0/128 (0.00%) 
Investigations     
Hospitalization for further diagnosis  1  1/193 (0.52%)  0/128 (0.00%) 
Metabolism and nutrition disorders     
Diabetic Ketoacidosis  1  0/193 (0.00%)  1/128 (0.78%) 
Renal and urinary disorders     
Renal Failure Acute  1  1/193 (0.52%)  0/128 (0.00%) 
1
Term from vocabulary, MedDRA (13.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
RHB-102 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   44/193 (22.80%)   19/128 (14.84%) 
Gastrointestinal disorders     
Abdominal Distension  1  3/193 (1.55%)  1/128 (0.78%) 
Abdominal Pain  1  3/193 (1.55%)  1/128 (0.78%) 
Constipation  1  9/193 (4.66%)  1/128 (0.78%) 
General disorders     
Chest Pain  1  2/193 (1.04%)  2/128 (1.56%) 
Pyrexia  1  3/193 (1.55%)  5/128 (3.91%) 
Nervous system disorders     
Dizziness  1  2/193 (1.04%)  2/128 (1.56%) 
Headache  1  22/193 (11.40%)  7/128 (5.47%) 
1
Term from vocabulary, MedDRA (13.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institution will provide to Sponsor, for review and comment, all manuscripts or other material prior to such publication. Sponsor shall have 30 days to review any such publication. The Sponsor can require changes to the communication and such confidential information shall be deleted and/or the submission of the proposed publication shall be delayed for an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Terry Plasse
Organization: RedHill Biopharma Ltd.
Phone: +972-(0)3-541-3131
EMail: terry@redhillbio.com
Layout table for additonal information
Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT02246439     History of Changes
Other Study ID Numbers: RHB-102-01
First Submitted: September 16, 2014
First Posted: September 22, 2014
Results First Submitted: November 30, 2018
Results First Posted: February 20, 2019
Last Update Posted: February 20, 2019