Investigation of Eluxadoline for Diabetic Diarrhea

NCT04313088 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 26347
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes is a chronic disease that affects a large part of the United States population. The majority of patients with diabetes will experience gastrointestinal symptoms. One of the most troublesome gastrointestinal symptoms that diabetes can cause is diarrhea, otherwise known as "Diabetic Diarrhea." This occurs because diabetes does damage to nerves that control the gut and prevent it from functioning normally. Currently, there are only several medications used to treat the symptoms of Diabetic Diarrhea, but many of these medications have serious side effects or do not work well. We are investigating the drug eluxadoline for the treatment of Diabetic Diarrhea. Eluxadoline is a gut-specific medication that is FDA approved to treat diarrhea related to irritable bowel syndrome (IBS-D). Our hypothesis is eluxadoline will safely and successfully reduce diarrhea symptoms (number of stools and less liquid stools) and improve the quality of life in patients with Diabetic Diarrhea when compared with placebo. Each patient with Diabetic Diarrhea who participates will take both eluxadoline and a placebo drug at separate times over a period of several months as part of a crossover study design. While on each medication, eluxadoline or placebo, the participants will keep a diary of symptoms and will be followed by the medical team through a combination of office visits and questionnaires. There will be five planned office visits and intermittent phone calls (questionnaires, surveys) over the 140-day study period. Participants will not be permitted to use any other anti-diarrhea medication during the study period and will continue on medication for management of their diabetes.

Conditions

Diabetic Diarrhea; Diabetes; Diarrhea

Keywords

eluxadoline; Viberzi

Outcome Measures

Primary Outcomes (1)

• Proportion of days with improved bowel movements

  Proportion of days in which all recorded bowel movements for that day have a consistency on the Bristol Stool Scale of \< 5. Scale: Type 1: Separate hard lumps, like nuts (hard to pass) Type 2: Sausage-shaped, but lumpy Type 3: Like a sausage but with cracks on its surface Type 4: Like a sausage or snake, smooth and soft Type 5: Soft blobs with clear cut edges (easy to pass) Type 6: Fluffy pieces with ragged edges, a mushy stool Type 7: Watery, no solid pieces, entirely liquid

  140 days

Secondary Outcomes (5)

• Likert score for global satisfaction

  140 days

• Diabetes quality of life

  140 days

• Diarrhea quality of life

  140 days

• Fecal incontinence

  140 days

• Nocturnal diarrhea

  140 days

Study Arms (2)

Experimental Group A

OTHER

All eligible patients will receive both eluxadoline and placebo, however each patient will be randomized to the order in which this happens. Eligible patients will be randomized 1:1 via random number generator to either receive eluxadoline 100mg twice daily then matching placebo or placebo then eluxadoline 100mg twice daily. Participants in Group A will take eluxadoline 100mg by mouth twice for 42 days. A washout phase will take place on days 43-70 where no study drug or placebo will be administered. On days 71-112, participants will crossover and take matching placebo by mouth twice daily. Each participant in Group A will take 42 days of eluxadoline 100mg twice daily followed by 42 days of placebo over the course the study.

Drug: Eluxadoline 100 mg

Experimental Group B

OTHER

All eligible patients will receive both eluxadoline and placebo, however each patient will be randomized to the order in which this happens. Eligible patients will be randomized 1:1 via random number generator to either receive eluxadoline 100mg twice daily then matching placebo or placebo then eluxadoline 100mg twice daily. Participants in Group B will take placebo by mouth twice daily for 42 days. A washout phase will take place on days 43-70 where no study drug or placebo will be administered. On days 71-112, participants will crossover and take eluxadoline 100mg by mouth twice daily. Each participant in Group B will take 42 days of placebo followed by 42 days of eluxadoline 100mg twice daily over the course the study.

Drug: Eluxadoline 100 mg

Interventions

Eluxadoline 100 mg DRUG

Eluxadoline 100mg by mouth twice daily with food

Also known as: Viberzi

Experimental Group A; Experimental Group B

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Documented diabetes mellitus (DM) Type I or DM Type II - must be on medical therapy
• ≥ 3 bowel movements per day with Bristol type 6 or 7 stools at least 4 days per week for \> 6 months. They must continue to meet these criteria during the 4 week pre-randomization phase.
• Normal sigmoidoscopy or colonoscopy with biopsies negative for microscopic colitis
• Negative work up for Clostridium difficile
• Negative work up for Celiac Disease either by assessment of serum tissue transglutaminase Immunoglobulin A (IgA) or by small bowel biopsy
• Normal fecal elastase and fecal calprotectin levels
• Normal thryoid stimulating hormone (TSH) level

You may not qualify if:

• Subjects who, in the estimation of the investigator, have drug-induced diarrhea
• Subjects unwilling to stop anti-diarrheal medications during the study
• Pregnancy or nursing mothers
• History of Cholecystectomy or Sphincter of Oddi Dysfunction
• Patients unable to undergo sigmoidoscopy or colonoscopy
• Patients with a history of inflammatory bowel disease (IBD)
• Prior history of pancreatitis
• Patients with hepatic impairment
• Patients who consume ≥ 3 alcoholic beverages per day
• Patients on oral opioids, who abuse illicit opioids, or have had a history of opioid abuse
• Patients on OATP1B1 Inhibitors (Rifampicin, Clarithromycin, Erythromycin, Cyclosporine, Gemfibrozil)
• Subjects unable to consent

Sponsors & Collaborators

• Temple University: lead
• Allergan: collaborator

Study Sites (1)

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

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MeSH Terms

Conditions

Diabetes Mellitus; Diarrhea

Interventions

eluxadoline

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Zachary Reichenbach, MD,PhD

  Lewis Katz School of Medicine at Temple University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization assignments will be handled by the statistician by means of a random number generator and assignments will be kept in opaque envelopes. The randomization scheme will be passed to the Temple Pharmacist. Based on the number, the Temple Pharmacist will dispense directly to the patient either drug or placebo in a labeled, child proof, pill bottle in a manner that does not disclose which group the patient is assigned. The Temple Pharmacist that is not a participant in the study will be responsible for dispensing study medication and will keep a secured log with the identity of that which is dispensed in case un-blinding becomes necessary.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible patients will be randomized 1:1 via random number generator to either receive eluxadoline 100mg twice daily (BID) or matching placebo. Participants will take assigned medication or placebo as prescribed for 42 days. A washout phase will take place on days 43-70. On days 71-112, participants will crossover and take either eluxadoline 100mg BID or matching placebo based on their previously assigned group. Throughout the study, weekly phone calls with a study coordinator will take place and participants will keep a daily stool diary. Office visits with a physician will take place at the beginning of the pre-randomization phase and at Day 0, 42, 70 and 112 of the study phase. Participants will refrain from use of all additional anti-diarrheal medication during the entirety of the study.

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 18, 2020
• Study Start: July 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)