Double-blind (neither physician nor patient knows of the actual treatment which can be with or without active substance), randomized (patient will be allocated to a certain treatment group by chance), placebo-controlled (tested against capsules without active substance), phase II dose-finding study comparing different doses of norursodeoxycholic acid capsules with placebo (without active substance) in the treatment of PSC (inflammation of the bile ducts with scar formation)

Conditions: primary sclerosing cholangitis
MedDRA version: 18.0Level: LLTClassification code 10036732Term: Primary sclerosing cholangitisSystem Organ Class: 100000004871
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2011-002754-31-DK

Lead Sponsor: Dr. Falk Pharma GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 160

Inclusion Criteria

1.Signed informed consent,
2.Male or female patients = 18 and < 80 years,
4.Alkaline Phosphatase = 1.5 x ULN at baseline,
6.Women of child-bearing potential have to apply during the entire duration of the study a highly effective method of birth control, which is defined as one which results in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, or some IUDs. Women of non-childbearing potential may be included if surgically sterile or post-menopausal for at least 2 years. The investigator is responsible for determining whether the subject has this adequate birth control for study participation.

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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.History or presence of other concomitant liver diseases including:
•Positive hepatitis B or C serology (Hbs Ag+, anti-HBc+, anti-HCV;
Note: Patients who present with anti-HBc+ only, may be included if they are HBV-DNA negative)
•Primary Biliary Cirrhosis, (AMA-positive)
•Wilson’s Disease
•Haemochromatosis
•Autoimmune Hepatitis
•Chronic alcoholic consumption (daily consumption >30g/d)
•Biopsy proven NASH
•Cholangiocarcinoma,
2.Treatment with any of the following drugs within the last 3 months prior to baseline: any glucocorticosteroids (including budesonide), azathioprine or other immunosuppressive drugs (e.g. cyclophosphamide, cyclosporine, methotrexate, tacrolimus, 6-mercaptopurine), chlorambucil, pentoxyfylline, penicillamine, pirfenidone, fibrates, biologics (e.g., anti-tumor necrosis factor-alpha therapy), or rifampicin,
5.Child B/C liver cirrhosis,
12.Total bilirubin > 3.0 mg/dl (> 51.3 µmol/L), at screening or baseline,
13.Both total bilirubin levels > ULN within the last 6 months prior to baseline and a rise of this level by more than 50% within the last 6 months prior to baseline,
14.Albumin < 36 g/L, at screening or baseline,
16.Any relevant systemic disease (e.g., AIDS),
17.Abnormal renal function (Cystatin C >1,15 X ULN) at screening and/or at baseline visit,
18.TSH > ULN at screening,
20.Any active malignant disease,
21.Known intolerance/hypersensitivity to study drug, or drugs of similar chemical structure or pharmacological profile

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of three doses of norUDCA vs. placebo for the treatment of PSC;<br><br>To identify efficacious norUDCA dose(s) for the treatment of PSC for further evaluation in phase III;Secondary Objective: To study safety and tolerability (adverse events, laboratory parameters) of norUDCA;<br><br>To assess quality of life;Primary end point(s): The primary endpoint is the change in serum alkaline phosphatase.;Timepoint(s) of evaluation of this end point: At the EOT visit.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary efficacy endpoints are:<br><br>· s-ALP at each study visit (screening to follow-up)<br><br>· ?-GT, AST, ALT and serum bilirubin levels at each study visit (screening to follow-up)<br><br>· Course of pruritus (measured by VAS): absolute change in the pruritus score from baseline to EOT, and from EOT to the follow-up visit;Timepoint(s) of evaluation of this end point: Timepoints of evaluation are included in the description of endpoints in E.5.2.