Bile-acid induced diarrhea in adult patients with Short Bowel Syndrome (SBS) MedDRA version: 20.1 Level: PT Classification code 10049416 Term: Short-bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders MedDRA version: 20.1 Level: LLT Classification code 10080049 Term: Bile acid diarrhea System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Enteric-Coated Cholestyramine (ECC) Capsules
Product Code: 37180
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: COLESTYRAMINE
CAS Number: 11041-12-6
Current Spo
Sponsors
Pharmascience Inc.
Eligibility
Sex/Gender
All
Inclusion 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: a. Non-surgical origin; OR b. 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: a. Mean daily production of at least 3 soft or watery stools (BSFS scores 6 or 7); or b. 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: a. Abstinence from heterosexual intercourse b. Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch) c. Intrauterine device (with or without hormones) d. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to investigate the clinical efficacy of new ECC capsules and select the most effective dose in adult patients with SBS.;Secondary Objective: The secondary objectives of this study are to evaluate the safety and tolerability of new ECC capsules in adult patients with SBS, and to evaluate the patients’ experience of related symptoms using a 11-point Visual Analog Scale (VAS).;Primary end point(s): Change in the weekly frequency of bowel movements measured between baseline and the second week of treatment ;Timepoint(s) of evaluation of this end point: Days 8 to 14, and Days 36 to 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Total number of bowel movements per week, after the first week of treatment 2) Total number of bowel movements for the whole 2-week treatment period 3) Mean daily stool form score according to the Bristol Stool Form Scale (BSFS), measured during the first week of treatment 4) Mean daily stool form score according to the BSFS, measured during the second week of treatment 5) Mean daily stool form score according to the BSFS, measured during the whole 2-week treatment period 6) Total number of bowel movements with a BSFS score = 6 during the first week of treatment 7) Total number of bowel movements with a BSFS score = 6 during the whole 2-week treatment period 8) Mean daily dose of loperamide in mg, if used, during the second week of treatment 9) Mean Diarrhea Composite Index ([weekly bowel movement frequency X mean daily BSFS score] + loperamide use [weekly mg X 3]) during the second week of treatment 10) Safety (to be evaluated through the assessment of adverse events (AE), laboratory tests, vital signs, ECG and physical examination) 11) Tolerability (to be evaluated through assessment of TEAEs and TESAEs) 12) Evaluation of severity of diarrhea, abdominal pain, urgency and bloating using an 11-point Visual Analog Scale (VAS);Timepoint(s) of evaluation of this end point: 1) Days 1 to 7, and Days 29 to 35 2) Days 1 to 14 and Days 29 to 42 3) Days 1 to 7, and Days 29 to 35 4) Days 8 to 14, and Days 36 to 42 5) Days 1 to 14 and Days 29 to 42 6) Days 1 to 7, and Days 29 to 35 7) Days 1 to 14 and Days 29 to 42 8) Days 8 to 14, and Days 36 to 42 9) Days 8 to 14, and Days 36 to 42 10) Throughout study 11) Throughout study 12) Days 0 (baseline), 15, 28 and 43 | — |
Countries
Poland
Contacts
Public ContactGlobal Specialty Pharma
Pharmascience Inc.
Outcome results
None listed