Patients with Bile Acid Malabsorption (BAM)/Bile Acid Diarrhoea (BAD)
Conditions
Interventions
Product Code: A3384
Pharmaceutical Form: Capsule
INN or Proposed INN: COLESTYRAMINE
CAS Number: 9007-26-5
Current Sponsor code: A3384
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Albireo AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Symptoms compatible with the diagnosis of Bile Acid Malabsorption/Bile Acid Diarrhoea (BAM/BAD) with onset >12 months prior to randomization; o SeHCAT 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 o A history of at least 3 liquid or soft stools ( BSFS =5) per day on average calculated from 7 days without therapy o The 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 =65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint is change from Baseline in # of BMs during the second treatment week (last 7 days of reporting).;Timepoint(s) of evaluation of this end point: The primary baseline period is defined as the last 7 days assessments recorded during Baseline period 2, prior to the first administration of study drug (Day 1). Timeponts of treatment is second treatment week (or last 7 days of reporting);Main Objective: The primary efficacy objective of this study is to demonstrate the efficacy of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period in patients with BAM, as determined by the # of bowel movements (BMs). The primary safety objective of this study is to assess the safety and tolerability of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period in patients with BAM, as determined by the occurrence of treatment-emergent SAEs. ;Secondary Objective: Secondary efficacy objectives of this study are to demonstrate the efficacy of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period on other BM parameters and BAM symptoms. Secondary safety objectives of this study include assessment of the safety and tolerability of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period, as determined by the occurrence of treatment-emergent AEs and changes in other safety parameters including laboratory tests and vital signs. Exploratory efficacy objectives of this study include assessments of serum concentrations of BAs and assessments of pharmacodynamic parameters of bile acid modulation such as C4 and FGF19. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints are: • Change from Baseline in average severity of diarrhoea during the second treatment week (last 7 days of reporting). • Change from Baseline in average severity of abdominal discomfort during the second treatment week (last 7 days of reporting). • Change from Baseline in average severity of abdominal bloating during the second treatment week (last 7 days of reporting). • Change from Baseline in average BSFS during the second treatment week (last 7 days of reporting). Explorative endpoints are: • Change from Baseline 2 in FGF19 at Visit 4 and Visit 5 • Change from Baseline 1 in FGF19 at Visit 4 • Change from Baseline 2 in C4 at Visit 4 and Visit 5 • Change from Baseline 1 in C4 at Visit 4 • Change from Baseline 2 in total s-BA at Visit 4 and Visit 5 • Change from Baseline 1 in total s-BA at Visit 4 ;Timepoint(s) of evaluation of this end point: The primary baseline period is defined as the last 7 days assessments recorded during Baseline period 2, prior to the first administration of study drug (Day 1). Timeponts of treatment is second treatment week (or last 7 days of reporting) | — |
Countries
Sweden, United Kingdom
Contacts
Public ContactResponsible Medical Officer
Albireo AB
Outcome results
None listed