Trial Outcomes & Findings for Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of BEKINDA (Ondansetron 12 mg Bimodal Release Tablets) for Diarrhea Predominant Irritable Bowel Syndrome (IBS-D) (NCT NCT02757105)
NCT ID: NCT02757105
Last Updated: 2018-08-28
Results Overview
A weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
COMPLETED
PHASE2
127 participants
8 weeks
2018-08-28
Participant Flow
Participant milestones
| Measure |
RHB-102
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
75
|
52
|
|
Overall Study
Treated
|
75
|
51
|
|
Overall Study
COMPLETED
|
63
|
41
|
|
Overall Study
NOT COMPLETED
|
12
|
11
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of BEKINDA (Ondansetron 12 mg Bimodal Release Tablets) for Diarrhea Predominant Irritable Bowel Syndrome (IBS-D)
Baseline characteristics by cohort
| Measure |
RHB-102
n=75 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=51 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
Total
n=126 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
71 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
53 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
58 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic/Latino
|
66 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
|
Median C-reactive protein (CRP)
|
2.07 mg/L
n=5 Participants
|
2.25 mg/L
n=7 Participants
|
2.09 mg/L
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Modified intent-to-treat (mITT) population analyzed included all patients who took at least one dose of double blinded study drug after randomization. In the mITT population, patients were analyzed by the treatment to which they were randomized. The population was used for a statistical analysis of efficacy endpoints.
A weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=75 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=51 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Stool Consistency Response Rate - mITT Population
Response
|
42 Participants
|
18 Participants
|
|
Summary and Analysis of Overall Stool Consistency Response Rate - mITT Population
Non-response
|
33 Participants
|
33 Participants
|
PRIMARY outcome
Timeframe: 8 weeksA weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=22 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=16 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Stool Consistency Response Rate Males - mITT Population
Response
|
11 Participants
|
5 Participants
|
|
Summary and Analysis of Overall Stool Consistency Response Rate Males - mITT Population
Non-response
|
11 Participants
|
11 Participants
|
PRIMARY outcome
Timeframe: 8 weeksA weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=53 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=35 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Stool Consistency Response Rate Females - mITT Population
Response
|
31 Participants
|
13 Participants
|
|
Summary and Analysis of Overall Stool Consistency Response Rate Females - mITT Population
Non-response
|
22 Participants
|
22 Participants
|
PRIMARY outcome
Timeframe: 8 weeksA weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=75 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=51 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Stool Consistency Response Rate: Sensitivity Analysis Without Imputation for Use of Rescue Medication - mITT Population
Response
|
43 Participants
|
19 Participants
|
|
Summary and Analysis of Overall Stool Consistency Response Rate: Sensitivity Analysis Without Imputation for Use of Rescue Medication - mITT Population
Non-response
|
32 Participants
|
32 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Patients with Baseline CRP \> Median
A weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=37 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=26 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP > Median - mITT Population
Response
|
22 Participants
|
6 Participants
|
|
Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP > Median - mITT Population
Non-response
|
15 Participants
|
20 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Patients with Baseline CRP ≤ Median
A weekly stool consistency responder was defined in the FDA guidance on IBS-D as a patient who experienced (during a week) a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 on the Bristol stool scale compared with baseline. In addition, to be considered a responder for the week, the patient could not have had an increase in average abdominal pain \>10% over baseline during that week. A patient was characterized as an overall stool consistency responder if the patient was a weekly responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=38 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=25 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP ≤ Median - mITT Population
Response
|
20 Participants
|
12 Participants
|
|
Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP ≤ Median - mITT Population
Non-response
|
18 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: 8 weeksA weekly pain responder was defined as a patient who experienced a decrease in the weekly average of worst abdominal pain in the past 24 hours score ≥30% compared with baseline and no increase in the number of days per week with Type 6 or 7 stool consistency. An overall pain responder was defined as a patient who was a weekly pain responder for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=75 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=51 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Worst Abdominal Pain Response Rate - mITT Population
Response
|
38 Participants
|
20 Participants
|
|
Summary and Analysis of Overall Worst Abdominal Pain Response Rate - mITT Population
Non-response
|
37 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: 8 weeksA patient was characterized as an overall weekly responder if the patient met both the stool consistency and pain response definitions for a given week. A patient was characterized as a composite study responder if the patient met the criteria for both weekly stool consistency and pain response for at least 50% of the planned weeks of treatment.
Outcome measures
| Measure |
RHB-102
n=75 Participants
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=51 Participants
1 tablet of matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Summary and Analysis of Overall Study Response Rate - mITT Population
Response
|
30 Participants
|
13 Participants
|
|
Summary and Analysis of Overall Study Response Rate - mITT Population
Non-response
|
45 Participants
|
38 Participants
|
Adverse Events
RHB-102
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
RHB-102
n=75 participants at risk
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
|
Placebo
n=51 participants at risk
1 tablet matching placebo, once daily for 8 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Constipation TEAE
|
13.3%
10/75 • 1 year, 2 months
|
3.9%
2/51 • 1 year, 2 months
|
|
Gastrointestinal disorders
Flatulence TEAE
|
8.0%
6/75 • 1 year, 2 months
|
0.00%
0/51 • 1 year, 2 months
|
|
Infections and infestations
Urinary Tract Infection TEAE
|
5.3%
4/75 • 1 year, 2 months
|
2.0%
1/51 • 1 year, 2 months
|
|
Investigations
Alanine aminotransferase increased TEAE
|
8.0%
6/75 • 1 year, 2 months
|
3.9%
2/51 • 1 year, 2 months
|
|
Investigations
Aspartate aminotransferase increased TEAE
|
8.0%
6/75 • 1 year, 2 months
|
9.8%
5/51 • 1 year, 2 months
|
|
Investigations
Blood creatinine increased TEAE
|
6.7%
5/75 • 1 year, 2 months
|
3.9%
2/51 • 1 year, 2 months
|
|
Investigations
Blood glucose increased TEAE
|
22.7%
17/75 • 1 year, 2 months
|
17.6%
9/51 • 1 year, 2 months
|
|
Investigations
Blood magnesium increased TEAE
|
6.7%
5/75 • 1 year, 2 months
|
3.9%
2/51 • 1 year, 2 months
|
|
Investigations
Blood potassium increased TEAE
|
6.7%
5/75 • 1 year, 2 months
|
3.9%
2/51 • 1 year, 2 months
|
|
Investigations
Blood sodium decreased TEAE
|
5.3%
4/75 • 1 year, 2 months
|
13.7%
7/51 • 1 year, 2 months
|
|
Investigations
Hemoglobin decreased TEAE
|
6.7%
5/75 • 1 year, 2 months
|
5.9%
3/51 • 1 year, 2 months
|
|
Investigations
Lymphocyte count decreased TEAE
|
6.7%
5/75 • 1 year, 2 months
|
9.8%
5/51 • 1 year, 2 months
|
|
Investigations
Protein urine present TEAE
|
36.0%
27/75 • 1 year, 2 months
|
33.3%
17/51 • 1 year, 2 months
|
|
Investigations
White blood cells urine positive TEAE
|
30.7%
23/75 • 1 year, 2 months
|
33.3%
17/51 • 1 year, 2 months
|
|
Investigations
pH urine increased TEAE
|
5.3%
4/75 • 1 year, 2 months
|
2.0%
1/51 • 1 year, 2 months
|
|
Nervous system disorders
Headache TEAE
|
9.3%
7/75 • 1 year, 2 months
|
11.8%
6/51 • 1 year, 2 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI agree that the Sponsor shall have the right to the first publication of the results of the Study. Following the first publication, the PI may publish data or results from the Study; subject to Sponsor for review and approval in writing at least sixty (60) days prior to the date of the publication. Sponsor may require changes and may extend the embargo to protect its intellectual property or other proprietary interests and to allow for the taking actions for this purpose.
- Publication restrictions are in place
Restriction type: OTHER