A trial of a new drug, obeticholic acid, in patients with diarrhoea caused by bile acids
- Conditions
- Bile acid diarrhoea (also known as bile acid malabsorption)Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2011-003777-28-GB
- Lead Sponsor
- Imperial College London and Imperial College Healthcare NHS Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 35
Patients aged 18 - 80 who present at routine Gastrointestinal Outpatient Clinics at Hammersmith and Charing Cross Hospitals with chronic diarrhoea, defined as an average stool frequency of at least three per day, of Bristol Stool Type 6 or 7, for at least 3 months. Previous routine SeHCAT testing to establish the presence or absence of bile acid diarrhoea (BAD) unless there is evidence of TI disease/ resection. BAD will be defined as SeHCAT 7-day retention of less than 15% or diarrhoea in presence of TI disease/ resection. Study subjects will be grouped as having secondary BAD, due to ileal resection or Crohn's disease, or primary BAD, with no obvious cause. The third, control group having chronic diarrhoea but with normal SeHCAT retention (greater than 15%).
Female patients must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use = 1 effective (= 1% failure rate) method of contraception during the trial and for 15 days after the last dose of OCA. Male subjects with female partners of childbearing potential must use = 1 effective method of contraception. Effective methods of contraception are considered to be: 1. Established use of oral, injected or implanted hormonal methods of contraception. 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. 4. Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 5. True abstinence: When this is in line with the preferred and usual lifestyle of the subject.
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
• Patients with other diagnoses leading to diarrhoea, including colorectal neoplasia, ulcerative colitis, coeliac disease, chronic pancreatitis, drug-induced diarrhoea or active infection.
• Patients who have not been investigated by standard clinical assessments to exclude these disorders.
• Treatment with bile acid sequestrants (colestyramine, colestipol, colesevelam) for 2 weeks before the first dose of OCA. Loperamide use will be allowed up to 16mg/d in divided doses.
• Previous biliary surgery, excluding cholecystectomy.
• Abnormal bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase on more than 1 occasion.
• Chronic liver disease
• Chronic kidney disease
• Active, serious medical disease with likely life expectancy less than 5 years
• Active substance abuse including inhaled or injection drugs in the year prior to screening
• Allergy to obeticholic acid.
• Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding. Pregnancy will be assessed with urinary ß-hCG pregnancy test.
• Participation in an investigational new drug trial in the 30 days before randomisation
• Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study
• Failure to give informed consent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to define the change over 2 weeks in serum fibroblast growth factor (FGF19) in 3 groups of patients: primary bile acid diarrhoea, secondary bile acid diarrhoea, and a control population of patients with chronic diarrhoea but with normal bile acid retention.;Secondary Objective: Secondary objectives are to study other markers of bile acid diarrhoea including 7a-hydroxy-4-cholesten-3-one, individual and total bile acids, and to assess tolerability and change in symptoms in the patient population.;Primary end point(s): The primary outcome measure is the change in fasting serum Fibroblast Growth Factor 19 (FGF19) after 2 weeks treatment with obeticholic acid. ;Timepoint(s) of evaluation of this end point: FGF19 measured on day 1 (at 0h before any dosing) and on day 15 (also at 0h).
- Secondary Outcome Measures
Name Time Method Secondary end point(s): FGF19 measured on day 1 and day 15 at hourly intervals up to 6h after oral dosing.<br>7aOHC4 measured from 0-6h on day 1 and day 15.<br>Total serum bile acids measured from 0-6h on day 1 and day 15.<br>Difference in bowel frequency and stool type between 7 days before first dose of the investigative agent (day -7 to -1), and from day 8-14.<br>Differences in use of rescue therapy (loperamide) for diarrhoea between day -7 to -1, and day 8-14.<br>Patient global assessment on day 1 and day 15.<br>Overall clinical assessment on day 1 and day 15.;Timepoint(s) of evaluation of this end point: Above