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)

• Register: EUCTR
• Last refreshed on: 8 February 2016
• Main ID: EUCTR2011-002754-31-FI
• Date of registration: 02/08/2012
• Prospective Registration: Yes
• Primary sponsor: Dr. Falk Pharma GmbH
• Public title: 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)
• Scientific title: Double-blind, randomized, placebo-controlled, phase II dose-finding study comparing different doses of norursodeoxycholic acid capsules with placebo in the treatment of primary sclerosing cholangitis - Norursodeoxycholic acid vs. Placebo in PSC
• Date of first enrolment: 19/10/2012
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002754-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Different dosages of IMP Number of treatment arms in the trial: 4

Countries of recruitment

Austria, Belgium, Denmark, Finland, Germany, Hungary, Lithuania, Netherlands, Norway, Spain, Sweden, United Kingdom

Contacts

• Name: Dept. of Clin. Res. & Development
• Affiliation: Dr. Falk Pharma GmbH

• Name: Dept. of Clin. Res. & Development
• Affiliation: Dr. Falk Pharma GmbH

Key inclusion & exclusion criteria

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 (> 50 µmol/L), at screening or baseline,
13. Rise in total bilirubin by at least 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

primary sclerosing cholangitis
MedDRA version: 17.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871

Intervention(s)

Product Name: norursodeoxycholic acid
Pharmaceutical Form: Capsule
INN or Proposed INN: norursodeoxycholic acid
CAS Number: 99697-24-2
Other descriptive name: NorUDCA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Main Objective: To evaluate the efficacy of three doses of norUDCA vs. placebo for the treatment of PSC;

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;

To assess quality of life

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints are:

· s-ALP at each study visit (screening to follow-up)

· ?-GT, AST, ALT and serum bilirubin levels at each study visit (screening to follow-up)

· 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.

Secondary ID(s)

NUC-3/PSC

2011-002754-31-DE

Source(s) of Monetary Support

Dr. Falk Pharma GmbH