A double-blind, randomized, placebo-controlled, study to demonstrate the efficacy and safety of 250 mg or 1 g A3384 administered orally twice daily for two weeks to patients with Bile Acid Malabsorption (BAM)/Bile Acid Diarrhoea (BAD)

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Digestive System Diseases [C06]; Patients with Bile Acid Malabsorption (BAM)/Bile Acid Diarrhoea (BAD)

• Registration Number: EUCTR2013-002924-17-GB
• Lead Sponsor: Albireo AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-03
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• Symptoms compatible with the diagnosis of Bile Acid Malabsorption/Bile Acid Diarrhoea (BAM/BAD) with onset >12 months prior to randomization;
oSeHCAT 7 day retention of less than 10% with measurement conducted within the last 36 months and no dramatic change in symptomatology since the SeHCAT assessment
oA history of at least 3 liquid or soft stools ( BSFS =5) per day on average calculated from 7 days without therapy
oThe last seven days before randomization having had >21 BMs of which >50% should be BSFS =5 (Evaluated pre-randomization at Visit 3)
•The patient reports having understood and has signed both the ICF and is willing to comply with all study visits and assessments;
•The patient is a male or non-pregnant female =18 years of age and =80 years of age with body mass index (BMI) =18.5 but <35;
•Having had a macroscopically normal colonoscopy with no histological signs of microscopic colitis within 5 years of screening.

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 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

•Any condition that, in the opinion of the Investigator constitutes a risk for the patient or a contraindication for participation and completion of the study, or could interfere with study objectives, conduct, or evaluations.
•An identified cause for BAM such as surgical intestinal resection or bypass, IBD or drug use
•Patients with other diagnoses leading to diarrhoea, including colorectal neoplasia, ulcerative colitis, coeliac disease, chronic pancreatitis or drug-induced diarrhoea.
•The patient has a structural abnormality of the GI tract or a disease or condition that can affect GI motility.
•The patient has a known, active, clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti infectives within 4 weeks of treatment start (study day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of screening period;
•The patient has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or hem-positive stool, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis.
•The patient has rectal bleeding and/or is hem-positive in the absence of known internal or external haemorrhoids.
•The patient has a history of cancer with last date of proven disease activity/presence of malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia, or carcinoma in situ of the skin or the cervix.
•Previous biliary surgery, excluding cholecystectomy.
•Other reason for diarrhoea such as pancreatitis, celiac disease, infection etc.
•Treatment with bile acid sequestrants (cholestyramine, colesevelam, colestipol or similar) after Baseline period 2 and before Visit 4.
•Treatment with loperamide or codeine after Visit 1 and before Visit 4.
•The patient has laboratory test levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) >2.5 x the upper limit of normal (ULN) or total bilirubin >1.5 x ULN
•Chronic liver or chronic kidney disease
•Active, serious medical disease with life expectancy less than 5 years
•Active substance abuse in the year before Screening
•Allergy to cholestyramine
•The patient has a history of a psychiatric disorder requiring hospitalization or suicide attempt in the 2 years prior to study inclusion;
•The patient has participated in any investigational clinical study within 30 days prior to Screening or within 5 half-lives of the investigated compound (whichever is longer) prior to Screening Baseline (unless the patient was never randomized to study treatment), or plans to participate in another clinical study during this study;
•The patient is a pregnant, breast-feeding or lactating female.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified