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

NCT02757105 | Completed Phase 2 Results

• 1 other identifier: RHB-102-02
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 16

Brief Summary

This is a randomized, double-blind, placebo-controlled, 2-arm parallel group study. After qualifying for the study and signing informed consent, patients will undergo a two-week observation period during which stool consistency and frequency data and symptom data will be collected. Patients will then be randomized 60:40 to RHB-102 12 mg (BEKINDA) or placebo. Patients will continue on treatment for 8 weeks. Each medication will be given once daily.

Conditions

Irritable Bowel Syndrome With Diarrhea

Outcome Measures

Primary Outcomes (6)

• Summary and Analysis of Overall Stool Consistency Response Rate - mITT Population

  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.

  8 weeks

• Summary and Analysis of Overall Stool Consistency Response Rate Males - mITT Population

  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.

  8 weeks

• Summary and Analysis of Overall Stool Consistency Response Rate Females - mITT Population

  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.

  8 weeks

• Summary and Analysis of Overall Stool Consistency Response Rate: Sensitivity Analysis Without Imputation for Use of Rescue Medication - mITT Population

  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.

  8 weeks

• Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP > Median - mITT Population

  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.

  8 weeks

• Summary and Analysis of Overall Stool Consistency Response Rate by Baseline CRP ≤ Median - mITT Population

  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.

  8 weeks

Secondary Outcomes (2)

• Summary and Analysis of Overall Worst Abdominal Pain Response Rate - mITT Population

  8 weeks

• Summary and Analysis of Overall Study Response Rate - mITT Population

  8 weeks

Study Arms (2)

Group A

EXPERIMENTAL

BEKINDA 12 mg (Ondansetron Bimodal Release Tablets), once daily for 8 weeks

Drug: BEKINDA

Group B

PLACEBO COMPARATOR

Placebo, once daily for 8 weeks

Drug: Placebo

Interventions

BEKINDA DRUG

Also known as: RHB-102 12 mg, Ondansetron Bimodal Release Tablet 12 mg

Group A

Placebo DRUG

Group B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients age≥18 years (with a minimum of 35% males in the study)
• Patient meets FDA guidance and Rome III criteria for IBS-D:
• a. Recurrent abdominal pain or discomfort over ≥6 months, with frequency ≥3 days/month in the last 3 months associated with ≥2 of the following: i. Improvement with defecation ii. Onset associated with a change in frequency of stool iii. Onset associated with a change in the form of stool b. Loose or watery stools (Bristol stool form scale 6 or 7) ≥2 days per week
• Average worst daily pain intensity ≥3.0 for each of the two baseline weeks
• Major laboratory parameters within the following limits (no worse than grade 1 abnormalities per NCI-CTCAE v4):
• a. Adequate hematologic function, as demonstrated by i. Hemoglobin ≥10 g/dL ii. Absolute neutrophil count (ANC) 1.5-10 x 10\^9/L iii. Platelets ≥100 x 10\^9/L b. Adequate liver and renal function as demonstrated by i. Aspartate transaminase (AST) and Alanine transaminase (ALT) each ≤ 3.0 x upper limit of normal (ULN) ii. Total bilirubin ≤1.5 x ULN iii. Creatinine ≤1.5 X ULN c. Euthyroid based on thyroid-stimulating hormone (TSH) and free T4 levels
• Patients on thyroid hormone replacement must be on a stable dose for at least one month prior to study entry.
• C-reactive protein ≤2 x ULN for lab
• Patients of childbearing potential and male patients with partners of childbearing potential must utilize effective contraceptive measures Women of childbearing potential are women who have menstruated in the past 12 months, with the exception of women who have undergone surgical sterilization
• All patients must sign informed consent.

You may not qualify if:

• Evidence of other cause for bowel disease:
• Relevant abnormalities seen on colonoscopy if previously performed or if required per this protocol. These include but are not limited to Crohn's disease, ulcerative colitis, diverticulitis, ischemic colitis, microscopic colitis.
• History of and/or positive serologic test for celiac disease
• Known or suspected lactose intolerance.
• History of abdominal surgery other than appendectomy or cholecystectomy at any time
• Any elective major surgery (of any organ) planned for the period of the study, including follow-up
• History of organic abnormalities of the GI tract including but not limited to intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, adhesions or impaired intestinal circulation (e.g., aortoiliac disease)
• Current or previous diagnosis of neoplasia (except non-GI neoplasia in complete remission ≥5 years, squamous and basal cell carcinomas). With approval of the medical monitor patients with curatively treated neoplasm in complete remission \<5 years may be entered in the study.
• Patients with a history of positive tests for ova or parasites or Clostridium difficile must be retested during the screening period and tests for the relevant agents must be negative
• Use of any 5-HT3 antagonist (5hydroxytryptamine receptor antagonists) within 4 weeks of the start of baseline data collection.
• Use of rifaximin within 4 months of the start of baseline data collection.
• Use of any other agent specific for IBS (such as alosetron or eluxadoline) or for symptomatic treatment of IBS (such as antispasmotics and antidiarrheals other than loperamide) within 2 weeks of the start of baseline data collection.
• Uses of any investigational agent for any indication within 4 weeks of the start of baseline data collection.
• Congestive heart failure, bradyarrhythmia (baseline pulse\<55/min), known long QT syndrome
• Patients who have Corrected QT interval (QTc) prolongation\>450 msec noted on screening ECG, or who are taking medication known to cause QT prolongation

Sponsors & Collaborators

• RedHill Biopharma Limited: lead

Study Sites (16)

Clinical Research Associates, LLC

Huntsville, Alabama, 35801, United States

Location

E Squared Research, Inc.

Huntsville, Alabama, 35801, United States

Location

Endoscoopy Center of AR

Little Rock, Arkansas, 72212, United States

Location

Arkansas Gastroenterology, P.A.

North Little Rock, Arkansas, 72117, United States

Location

Prx Clinical

Garden Grove, California, 92840, United States

Location

Providence Clinical Research

North Hollywood, California, 91606, United States

Location

Shahram Jacobs MD, Inc.

Sherman Oaks, California, 91403, United States

Location

Advanced Rx Clinical Research Group, Inc.

Westminster, California, 92683, United States

Location

Bristol Hospital Dba Connecticut Gastroenterology Institute

Bristol, Connecticut, 06010, United States

Location

Clinical Research of Homestead

Homestead, Florida, 33030, United States

Location

PMG Research of Winston-Salem

Winston-Salem, North Carolina, 27103, United States

Location

Great Lakes Medical Research

Mentor, Ohio, 44060, United States

Location

Clinsearch

Chattanooga, Tennessee, 37421, United States

Location

New Phase Research & Development

Knoxville, Tennessee, 37909, United States

Location

Aztec Medical Research, LLC

Channelview, Texas, 77530, United States

Location

Gastroenterology Research of San Antonio

San Antonio, Texas, 78229, United States

Location

Results Point of Contact

• Title: Dr. Terry F. Plasse
• Organization: RedHill Biopharma Ltd.

terry@redhillbio.com

972-(0)3-541-3131

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: April 29, 2016
• Study Start: May 19, 2016
• Primary Completion: June 16, 2017
• Study Completion: July 14, 2017
• Last Updated: August 28, 2018
• Results First Posted: July 31, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)