Bile acid diarrhoea (also known as bile acid malabsorption) MedDRA version: 20.1 Level: LLT Classification code 10080051 Term: Bile acid diarrhoea System Organ Class: 100000004856
Conditions
Interventions
Trade Name: Ocaliva
Product Name: Ocaliva
Product Code: N/A
Pharmaceutical Form: Tablet
INN or Proposed INN: Obeticholic acid
CAS Number: 459789-99-2
Current Sponsor code: INT-747
Other descriptive na
Sponsors
Imperial College Healthcare NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female subjects aged between 18 and 80 years old. • Previously diagnosed with Primary Bile Acid Diarrhoea in the moderate or severe range, with a SeHCAT test 7d retention = 10%. • Presence of = 14 stools/week, with = 25% of stools being Bristol Stool Form Scale (BSFS) Type 6 or 7. These criteria need to be confirmed by daily symptom diary during screening. • Subjects must be willing and able to give written informed consent and agree to comply with the study protocol. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Presence of another medical condition known to cause chronic diarrhoea (such as coeliac disease, colorectal neoplasia, inflammatory bowel disease, microscopic colitis, chronic pancreatitis, drug-induced diarrhea, active gastrointestinal infection) or insufficient investigations to exclude these. • Resection of small or large intestine >10cm. • Cholecystectomy, unless diarrhoeal symptoms were present for at least 1 year before the surgery. • Biliary surgery or gastric bypass. • Treatment with bile acid sequestrants (BAS) including Colestyramine, Colestipol or Colesevelam within 4 weeks of randomisation. • Use of opiate medications. Loperamide use is permitted in divided doses up to 16 mg/day. • Acute or chronic kidney disease with serum creatinine = 180 µmol/L at screening. • Concomitant liver disease, except mild NAFLD. • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase > 2x upper limit of normal (ULN) at screening. • Total bilirubin >1x ULN at screening; except that patients with Gilbert’s syndrome with elevated total bilirubin may be enrolled, provided that direct (conjugated) bilirubin levels are within normal limits. • Confirmed abnormal platelet levels of 450,000 platelets/mL. • Known or suspected use of illicit drugs or drugs of abuse within 1 year. • Pregnancy, planned pregnancy, potential for pregnancy (such as unwillingness to use effective birth control during the study), or breast feeding. • Use of an investigational new drug within 30 days (or 5 elimination half-lives) prior to screening. • History of allergy to any of the ingredients in the investigational medications. • Any other medical condition or social circumstance, which in the opinion of the investigator would impede compliance with or hinder completion of the study • Inability to comply with the protocol or give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to see if there is any difference in the change in bowel function (measured by a index composed of the number of stools, their type, and use of any rescue medication, taken over 7 days) between the baseline and on week 6 of treatment. We will compare patients on Obeticholic acid, either 10mg or 25mg once daily, or an identical placebo. Patients, and their research team, will not know which medication they have been randomly assigned to take.;Secondary Objective: • Comparison of the effects on bowel function index with 10mg and 25mg doses of OCA, at 2, 4 and 6 weeks • Comparison of the changes in bowel function index with OCA 25mg after 6 and 12 weeks treatment • Comparison of the changes in bowel function index with OCA 10mg for 6 weeks, followed by 25mg for 6 weeks, after 12 weeks total treatment • Changes in need for rescue medication • Changes in individual symptoms of stool frequency, stool type, faecal urgency, incontinence, abdominal pain, and bloating at 2, 4, 6 and 12 weeks • Changes in overall quality of life at 2, 4, 6 and 12 weeks • Proportion of subjects in each group meeting the FDA definition of a weekly responder: a decrease at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7, compared with baseline. • Relationship of response to severity of BAD (i.e. SeHCAT <5% vs. 5-10%) • Changes in specific biomarkers (serum FGF19, C4, total bile acids, faecal calprotectin). • Tolerabil;Primary end point(s): • The difference in change in bowel function, measured by a composite index of stool frequency, stool type and rescue medication over 7 days, between baseline and week 6 of treatment with OCA, either 10mg or 25mg od, compared with placebo.;Timepoint(s) of evaluation of this end point: Week 6 of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Comparison of the changes in bowel function index with OCA 10mg after 6 and 12 weeks treatment • Comparison of the effects on bowel function index with 10mg and 25mg doses of OCA, at 2, 4 and 6 weeks • Changes in need for rescue medication (loperamide) • Changes in individual symptoms of stool frequency, stool type, faecal urgency, incontinence, abdominal pain, and bloating at 2, 4, 6 and 12 weeks • Changes in overall quality of life at 2, 4, 6 and 12 weeks • Proportion of subjects in each group meeting the FDA definition of a weekly responder: a decrease at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline. • Relationship of response to severity of BAD (i.e. SeHCAT <5% vs. 5-10%) • Changes in specific biomarkers (serum FGF19, C4, total bile acids, faecal calprotectin). • Tolerability and frequency of side-effects over the duration of the trial. ;Timepoint(s) of evaluation of this end point: As above | — |
Countries
United Kingdom
Outcome results
None listed