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Trial record 9 of 12 for:    RedHill Biopharma

Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of BEKINDA (Ondansetron 12 mg Bimodal Release Tablets) for Diarrhea Predominant Irritable Bowel Syndrome (IBS-D)

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ClinicalTrials.gov Identifier: NCT02757105
Recruitment Status : Completed
First Posted : April 29, 2016
Results First Posted : July 31, 2018
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Irritable Bowel Syndrome With Diarrhea
Interventions Drug: BEKINDA
Drug: Placebo
Enrollment 127
Recruitment Details  
Pre-assignment Details  
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description 1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks 1 tablet of matching placebo, once daily for 8 weeks
Period Title: Overall Study
Started 75 52
Treated [1] 75 51
Completed [2] 63 41
Not Completed 12 11
[1]
1 patient in the placebo group was randomized and not treated.
[2]
At least 7.6 weeks of treatment & end of study visit 28 +/- 11 days after last intake of study drug.
Arm/Group Title RHB-102 Placebo Total
Hide Arm/Group Description 1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks 1 tablet of matching placebo, once daily for 8 weeks Total of all reporting groups
Overall Number of Baseline Participants 75 51 126
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 51 participants 126 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
71
  94.7%
49
  96.1%
120
  95.2%
>=65 years
4
   5.3%
2
   3.9%
6
   4.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 51 participants 126 participants
Female
53
  70.7%
35
  68.6%
88
  69.8%
Male
22
  29.3%
16
  31.4%
38
  30.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 51 participants 126 participants
American Indian or Alaskan Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
11
  14.7%
6
  11.8%
17
  13.5%
Black or African American
5
   6.7%
3
   5.9%
8
   6.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
White
58
  77.3%
42
  82.4%
100
  79.4%
Other
1
   1.3%
0
   0.0%
1
   0.8%
Hispanic/Latino
9
  12.0%
4
   7.8%
13
  10.3%
Not Hispanic/Latino
66
  88.0%
47
  92.2%
113
  89.7%
Median C-reactive protein (CRP)  
Measure Type: Number
Unit of measure:  mg/L
Number Analyzed 75 participants 51 participants 126 participants
2.07 2.25 2.09
1.Primary Outcome
Title Summary and Analysis of Overall Stool Consistency Response Rate - mITT Population
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet of matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 75 51
Measure Type: Count of Participants
Unit of Measure: Participants
Response
42
  56.0%
18
  35.3%
Non-response
33
  44.0%
33
  64.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
2.Primary Outcome
Title Summary and Analysis of Overall Stool Consistency Response Rate Males - mITT Population
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet of matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 22 16
Measure Type: Count of Participants
Unit of Measure: Participants
Response
11
  50.0%
5
  31.3%
Non-response
11
  50.0%
11
  68.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.410
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
3.Primary Outcome
Title Summary and Analysis of Overall Stool Consistency Response Rate Females - mITT Population
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 53 35
Measure Type: Count of Participants
Unit of Measure: Participants
Response
31
  58.5%
13
  37.1%
Non-response
22
  41.5%
22
  62.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
4.Primary Outcome
Title Summary and Analysis of Overall Stool Consistency Response Rate: Sensitivity Analysis Without Imputation for Use of Rescue Medication – mITT Population
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 75 51
Measure Type: Count of Participants
Unit of Measure: Participants
Response
43
  57.3%
19
  37.3%
Non-response
32
  42.7%
32
  62.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
5.Primary Outcome
Title Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP > Median – mITT Population
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with Baseline CRP > Median
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet of matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 37 26
Measure Type: Count of Participants
Unit of Measure: Participants
Response
22
  59.5%
6
  23.1%
Non-response
15
  40.5%
20
  76.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
6.Primary Outcome
Title Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP ≤ Median – mITT Population
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with Baseline CRP ≤ Median
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet of matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 38 25
Measure Type: Count of Participants
Unit of Measure: Participants
Response
20
  52.6%
12
  48.0%
Non-response
18
  47.4%
13
  52.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.919
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
7.Secondary Outcome
Title Summary and Analysis of Overall Worst Abdominal Pain Response Rate – mITT Population
Hide Description A 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 75 51
Measure Type: Count of Participants
Unit of Measure: Participants
Response
38
  50.7%
20
  39.2%
Non-response
37
  49.3%
31
  60.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 11.5
Confidence Interval (2-Sided) 95%
-7.7 to 30.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Summary and Analysis of Overall Study Response Rate – mITT Population
Hide Description A 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description:
1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks
1 tablet matching placebo, once daily for 8 weeks
Overall Number of Participants Analyzed 75 51
Measure Type: Count of Participants
Unit of Measure: Participants
Response
30
  40.0%
13
  25.5%
Non-response
45
  60.0%
38
  74.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RHB-102, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14.5
Confidence Interval (2-Sided) 95%
-3.4 to 32.5
Estimation Comments [Not Specified]
Time Frame 1 year, 2 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title RHB-102 Placebo
Hide Arm/Group Description 1 tablet containing 3 mg immediate release and 9 mg sustained release ondansetron, once daily for 8 weeks 1 tablet matching placebo, once daily for 8 weeks
All-Cause Mortality
RHB-102 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/75 (0.00%)   0/51 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
RHB-102 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/75 (0.00%)   0/51 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.0%
RHB-102 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   68/75 (90.67%)   47/51 (92.16%) 
Gastrointestinal disorders     
Constipation TEAE * 1  10/75 (13.33%)  2/51 (3.92%) 
Flatulence TEAE * 1  6/75 (8.00%)  0/51 (0.00%) 
Infections and infestations     
Urinary Tract Infection TEAE * 1  4/75 (5.33%)  1/51 (1.96%) 
Investigations     
Alanine aminotransferase increased TEAE * 1  6/75 (8.00%)  2/51 (3.92%) 
Aspartate aminotransferase increased TEAE * 1  6/75 (8.00%)  5/51 (9.80%) 
Blood creatinine increased TEAE * 1  5/75 (6.67%)  2/51 (3.92%) 
Blood glucose increased TEAE * 1  17/75 (22.67%)  9/51 (17.65%) 
Blood magnesium increased TEAE * 1  5/75 (6.67%)  2/51 (3.92%) 
Blood potassium increased TEAE * 1  5/75 (6.67%)  2/51 (3.92%) 
Blood sodium decreased TEAE * 1  4/75 (5.33%)  7/51 (13.73%) 
Hemoglobin decreased TEAE * 1  5/75 (6.67%)  3/51 (5.88%) 
Lymphocyte count decreased TEAE * 1  5/75 (6.67%)  5/51 (9.80%) 
Protein urine present TEAE * 1  27/75 (36.00%)  17/51 (33.33%) 
White blood cells urine positive TEAE * 1  23/75 (30.67%)  17/51 (33.33%) 
pH urine increased TEAE * 1  4/75 (5.33%)  1/51 (1.96%) 
Nervous system disorders     
Headache TEAE * 1  7/75 (9.33%)  6/51 (11.76%) 
1
Term from vocabulary, MedDRA 13.1
*
Indicates events were collected by non-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.
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.
Results Point of Contact
Name/Title: Dr. Terry F. Plasse
Organization: RedHill Biopharma Ltd.
Phone: 972-(0)3-541-3131
Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT02757105     History of Changes
Other Study ID Numbers: RHB-102-02
First Submitted: April 27, 2016
First Posted: April 29, 2016
Results First Submitted: June 15, 2018
Results First Posted: July 31, 2018
Last Update Posted: August 28, 2018