Effects of Eluxadoline (Viberzi®) 100 mg Twice Daily on Diarrhea-Associated Fecal Incontinence

NCT03489265 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 17-1561895
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Accidental bowel leakage (fecal incontinence) increases in people who have diarrhea and sensations of urgency to have a bowel movement. Drugs such as loperamide (Imodium) that reduce diarrhea improve accidental bowel leakage, but loperamide has disadvantages: it is difficult to find a dose that does not cause constipation, and it does not reduce urge sensations. Eluxadoline is a new drug that is effective for reducing diarrhea, abdominal pain, and urgency in patients with irritable bowel syndrome, and it may be less likely than loperamide to cause severe constipation. Therefore, eluxadoline may help patients manage accidental bowel leakage caused by diarrhea. The chemical name for Viberzi® is eluxadoline. The primary aims of this study are to find out if eluxadoline at a dose of 100 mg orally twice a day will reduce the average number of days the patient has accidental bowel leakage, and to see if the rate of accidental bowel leakage increases when the patient stops taking eluxadoline. Additional goals are to find out if eluxadoline decreases diarrhea and urge sensations. This is a small (pilot) study to show whether eluxadoline is an effective way of treating accidental bowel leakage. If the study shows this, a larger study will be needed. There are three phases to this 12-week study: (1) A two-week run-in period to see if the patient meets the inclusion criteria. (2) Two months for treatment including one month on eluxadoline and one on placebo (sugar pills) twice a day. (3) A two-week follow-up to see what happens when you stop taking eluxadoline. To participate in the study, patients should be aged 18 or older. Patients with inflammatory bowel disease, anal fissures, or congenital malformations will be excluded. The primary outcome is the average number of days per week with any solid or liquid bowel accidents. Additional information includes: (1) Number of days per week the patient takes loperamide, (2) days per week with loose or watery stools, (3) days per week with moderate to strong urge sensations, and (4) questionnaires to measure the severity of accidental bowel leakage, quality of life, anxiety, and depression. There will be up to 38 patients in the study.

Conditions

Fecal Incontinence; Accidental Bowel Leakage; Anal Incontinence; Diarrhea; Urge Incontinence

Outcome Measures

Primary Outcomes (4)

• Run-in days per week with fecal incontinence

  If there are less than 5 days in a 7-day period that have complete diary data, the subject will be excluded. The number of days per week with fecal incontinence (i.e., a score \>0) will be counted and divided by 7 to obtain a rate per week. The range of scores is 0 to 7 with 7 being the most severe fecal incontinence.

  Baseline Period, starting on Day 1 and ending at the conclusion of Day 14

• Treatment Period 1 days per week with fecal incontinence

  If there are less than 5 days in a 7-day period that have complete diary data in weeks 5 and 6, the Treatment Period 1 variable will be missing. The number of days per week with fecal incontinence (i.e., a score \>0) will be counted and divided by 7 to obtain a rate per week. The range of scores is 0 to 7 with 7 being the most severe fecal incontinence.

  Treatment Period 1 (measured across Weeks 5 and 6)

• Treatment Period 2 days per week with fecal incontinence

  If there are less than 5 days in a 7-day period that have complete diary data in weeks 9 and 10, the Treatment Period 2 variable is missing. The number of days per week with fecal incontinence (i.e., a score \>0) will be counted and divided by 7 to obtain a rate per week. The range of scores is 0 to 7 with 7 being the most severe fecal incontinence.

  Treatment Period 2 (measured across Weeks 9 and 10)

• Follow-up days per week with fecal incontinence

  If there are less than 5 days in a 7-day period that have complete diary data in weeks 11 and 12, the Follow-Up variable is missing. The number of days per week with fecal incontinence (i.e., a score \>0) will be counted and divided by 7 to obtain a rate per week. The range of scores is 0 to 7 with 7 being the most severe fecal incontinence.

  Follow-up period (measured across Weeks 11 and 12)

Secondary Outcomes (12)

• Days per week with loperamide (escape medication)

  Weeks 1, 2, 5, 6, 9, 10, 11, and 12

• Days per week patient described bowel movements as 6 or 7 on the Bristol Stool Scale

  Weeks 1, 2, 5, 6, 9, 10, 11, and 12

• Days per week patient reported strong urge sensations

  Weeks 1, 2, 5, 6, 9, 10, 11, and 12

• Fecal Incontinence Severity Score (FISS) over time

  Weeks 2, 6,10, and 12

• Fecal Incontinence Quality of Life Scale Score for Lifestyle (FIQOL-Lifestyle)

  Weeks 2, 6, 10, and12

Study Arms (2)

Eluxadoline followed by Placebo

OTHER

Following a 2-week run-in period, patients will receive Eluxadoline 100 mg twice daily for 4 weeks then placebo tablets taken twice daily for 4 weeks followed by a 2-week follow-up period during which placebo will be administered twice daily.

Drug: Eluxadoline 100 mg; Other: Placebo

Placebo followed by Eluxadoline

OTHER

Following a 2-week run-in period, patients will receive placebo twice daily for 4 weeks then Eluxadoline 100 mg twice daily for 4 weeks followed by a 2-week follow-up period during which placebo will be administered twice daily.

Drug: Eluxadoline 100 mg; Other: Placebo

Interventions

Eluxadoline 100 mg DRUG

100 mg capsule-shaped tablet by mouth taken twice per day

Also known as: Viberzi®

Eluxadoline followed by Placebo; Placebo followed by Eluxadoline

Placebo OTHER

Matching capsule-shaped placebo tablets taken by mouth twice per day

Also known as: sugar pill

Eluxadoline followed by Placebo; Placebo followed by Eluxadoline

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age.
• Any gender, race, or ethnicity.
• Must self-report an average of at least 2 episodes of solid or liquid FI per week for the previous month.
• Must self-report an average of at least 2 bowel movements (BMs) per week that are Bristol Types 6 or 7 (mushy or liquid stools).
• Subjects must have access to the internet at home and be willing to enter symptom data each night before sleeping.

You may not qualify if:

• Patients with inflammatory bowel disease, anal fissure, or congenital malformations as a cause of FI will be excluded.
• Subjects who start the study and do not experience at least 4 episodes of solid or liquid FI and at least 4 BMs that are Bristol Stool types 6 or 7 during the first two weeks will be withdrawn from the study.
• Subjects who do not provide at least 4 days of valid stool diary data per week during the first two weeks will be withdrawn from the study.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Allergan: collaborator

Related Publications (11)

• Whitehead WE, Borrud L, Goode PS, Meikle S, Mueller ER, Tuteja A, Weidner A, Weinstein M, Ye W; Pelvic Floor Disorders Network. Fecal incontinence in US adults: epidemiology and risk factors. Gastroenterology. 2009 Aug;137(2):512-7, 517.e1-2. doi: 10.1053/j.gastro.2009.04.054. Epub 2009 May 4.

  PMID: 19410574 BACKGROUND

• Bharucha AE, Zinsmeister AR, Locke GR, Seide BM, McKeon K, Schleck CD, Melton LJ 3rd. Risk factors for fecal incontinence: a population-based study in women. Am J Gastroenterol. 2006 Jun;101(6):1305-12. doi: 10.1111/j.1572-0241.2006.00553.x.

  PMID: 16771954 BACKGROUND

• Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med. 2016 Jan 21;374(3):242-53. doi: 10.1056/NEJMoa1505180.

  PMID: 26789872 BACKGROUND

• Simren M, Palsson OS, Heymen S, Bajor A, Tornblom H, Whitehead WE. Fecal incontinence in irritable bowel syndrome: Prevalence and associated factors in Swedish and American patients. Neurogastroenterol Motil. 2017 Feb;29(2):10.1111/nmo.12919. doi: 10.1111/nmo.12919. Epub 2016 Aug 31.

  PMID: 27581702 BACKGROUND

• Sun WM, Read NW, Verlinden M. Effects of loperamide oxide on gastrointestinal transit time and anorectal function in patients with chronic diarrhoea and faecal incontinence. Scand J Gastroenterol. 1997 Jan;32(1):34-8. doi: 10.3109/00365529709025060.

  PMID: 9018764 BACKGROUND

• Sjodahl J, Walter SA, Johansson E, Ingemansson A, Ryn AK, Hallbook O. Combination therapy with biofeedback, loperamide, and stool-bulking agents is effective for the treatment of fecal incontinence in women - a randomized controlled trial. Scand J Gastroenterol. 2015 Aug;50(8):965-74. doi: 10.3109/00365521.2014.999252. Epub 2015 Apr 20.

  PMID: 25892434 BACKGROUND

• Palmer KR, Corbett CL, Holdsworth CD. Double-blind cross-over study comparing loperamide, codeine and diphenoxylate in the treatment of chronic diarrhea. Gastroenterology. 1980 Dec;79(6):1272-5.

  PMID: 7002706 BACKGROUND

• Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9.

  PMID: 23583433 BACKGROUND

• Noelting J, Zinsmeister AR, Bharucha AE. Validating endpoints for therapeutic trials in fecal incontinence. Neurogastroenterol Motil. 2016 Aug;28(8):1148-56. doi: 10.1111/nmo.12809. Epub 2016 Mar 6.

  PMID: 26948292 BACKGROUND

• Rockwood TH, Church JM, Fleshman JW, Kane RL, Mavrantonis C, Thorson AG, Wexner SD, Bliss D, Lowry AC. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum. 2000 Jan;43(1):9-16; discussion 16-7. doi: 10.1007/BF02237236.

  PMID: 10813117 BACKGROUND

• Read M, Read NW, Barber DC, Duthie HL. Effects of loperamide on anal sphincter function in patients complaining of chronic diarrhea with fecal incontinence and urgency. Dig Dis Sci. 1982 Sep;27(9):807-14. doi: 10.1007/BF01391374.

  PMID: 7105952 BACKGROUND

Related Links

• Link to Eluxadoline (Viberzi) Patient Information Guide and full prescribing information provided by Allergan

MeSH Terms

Conditions

Fecal Incontinence; Encopresis; Diarrhea; Urinary Incontinence, Urge

Interventions

eluxadoline; Sugars

Condition Hierarchy (Ancestors)

Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Elimination Disorders; Mental Disorders; Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• William (Bill) Whitehead, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients will not be aware when Eluxadoline or Placebo are administered. Investigators will be masked to whether Eluxadoline is given in Treatment Period 1 or Treatment Period 2 unless there is an adverse event that requires unmasking the treatment for this patient to ascertain whether the adverse event is drug-related.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized to 1 of 2 sequences. Each sequence includes 4 periods: Run-in, Treatment Period 1, Treatment Period 2, and Follow-Up. In Sequence A, Eluxadoline will be given 100 mg BID in Treatment Period 1 and Placebo will be given in Treatment Period 2. In Sequence B, Placebo will be given in Treatment Period 1 and Eluxadoline will be given in Treatment Period 2. Placebo will be given during Baseline and Follow-Up of both arms.

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: April 5, 2018
• Study Start: April 1, 2019
• Primary Completion: September 1, 2019
• Study Completion: March 1, 2020
• Last Updated: July 25, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR, ANALYTIC CODE
• Time Frame: 9-36 months following publication of the study results.
• Access Criteria: Requester must have approval from an Institutional Review Board (IRB), Independent Ethics Committee (IED), or Research Ethics Board (REB), and requester has executed an acceptable data use/sharing agreement with UNC.