Efficacy, Safety and Tolerability of Enteric-Coated Cholestyramine Capsules for Adult Short Bowel Syndrome
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Syndrome
Intervention: Enteric-Coated Cholestyramine (ECC) Capsule; Placebo
Intervention description: Enteric-Coated Delayed Release Cholestyramine Capsules; Enteric-Coated Delayed Release Placebo Capsules
Intervention MeSH terms: Cholestyramine Resin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Multiple-center, randomized, double-blind, double dummy, 2-period, 2-sequence cross-over design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This study will be fully blinded, using the double dummy technique (combination of active ECC capsules and matching placebo in the low dose treatment arm).
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      A new Enteric-Coated Cholestyramine (ECC) capsule has been developed to manage diarrhea
      associated with Short Bowel Syndrome (SBS) in adults. The formulation is expected to release
      cholestyramine in the remaining segment of the small intestine in SBS patients, thus binding
      bile acids after fat digestion, but before induction of diarrhea in the colon. The
      delayed-release profile is also expected to help reduce the potential for drug-drug
      interactions occurring in the proximal small intestine. Two doses of ECC will be studied for
      efficacy, safety and tolerability in this Phase IIa trial.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult, ambulatory male and female subjects

          2. Provision of signed and dated informed consent form (ICF)

          3. Age ≥ 18 years and ≤ 80 years

          4. Stable SBS of:

               1. Non-surgical origin; OR

               2. Surgical origin where the last surgical ileal resection was performed at least 6
                  months prior to enrolment

          5. Partial, Home Parenteral Nutrition and/or parenteral fluids are allowed, at a maximum
             frequency of 6 times a week throughout the trial, as long as the regimen has been
             stable for at least 2 weeks prior to screening and is expected to remain unchanged
             during the study

          6. At least 50 % of the colon being intact

          7. Intact duodenum

          8. BMI ≥ 18

          9. Presence of stable chronic diarrhea for at least 3 months prior to enrolment as
             evidenced by medical history

         10. Presence of stable chronic diarrhea during the 2-week screening diary period before
             randomization, as evidenced by completion of a screening diary demonstrating:

               1. Mean daily production of at least 3 soft or watery stools (BSFS scores 6 or 7);
                  or

               2. More than 3 bowel movements per day on average with >25% of them being BSFS type
                  6 or 7

         11. Stated willingness and ability to comply with all study procedures, including daily
             recording of bowel movements and BSFS in the patient diaries, and availability for the
             duration of the study

         12. Clinical laboratory values within the laboratory's stated normal range; if not within
             this range, they must be without clinical significance, as determined by the
             investigator

         13. Female subjects must meet one of the following criteria:

             a) Participant is of childbearing potential and agrees to use one of the accepted
             contraceptive regimens from at least 30 days prior to the first study treatment
             administration through to at least 30 days after the last dose of the study treatment.
             An acceptable method of contraception includes one of the following:

               1. Abstinence from heterosexual intercourse

               2. Systemic contraceptives (combined birth control pills,
                  injectable/implant/insertable hormonal birth control products, transdermal patch)

               3. Intrauterine device (with or without hormones)

               4. Condom with spermicide

             b) Participants of non-childbearing potential, defined as surgically sterile (i.e. has
             undergone complete hysterectomy or bilateral oophorectomy) or is in a menopausal state
             (i.e. at least 1 year without menses prior to the first study drug administration) are
             eligible

        Exclusion Criteria:

          1. Patients with known or suspected intestinal strictures of clinical relevance as judged
             by the Investigator

          2. Active inflammatory bowel disease (IBD) or fistula during the screening period as
             judged by the Investigator

          3. Crohn's disease patients not being in clinical remission for the last 12 weeks prior
             to randomization

          4. Diarrhea caused by other causes than SBS

          5. Presence of clinically significant steatorrhea, requiring pancreatic enzymes
             supplementation

          6. Presence of complete biliary obstruction

          7. Presence of active cancer (except resected cutaneous basal or squamous cell carcinoma
             and except in situ cervical cancer) and/or need to receive chemotherapy or
             radiotherapy during the study

          8. History of allergic reaction to cholestyramine or any excipient of the investigational
             drug product or placebo, or packaging components

          9. Females who are lactating at screening

         10. Females who are pregnant according to the pregnancy test at screening or prior to the
             first study treatment administration

         11. Significant history (at least 3 consecutive months in the year prior to Screening) of
             drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive
             alcohol, acute or chronic)

         12. Subjects who took an Investigational Product (IP) in the 30 days prior to the first
             study drug administration

         13. Any other clinically significant condition that is considered by the principal
             investigator as being susceptible to put the patient at greater safety risk, influence
             response to study product, or interfere with study assessments.