Primary:* To evalaute 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:* To study safety and tolerability (…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean relative change (%) of serum alkaline phosphatase (sALP) between baselien
visit and EOT visit (last observation carried forward).
Secondary outcome
Proportion of patients with at least 50 % reduction in s-ALP between baseline
and EOT (LOCF)
Proportion of patients with normalisation of s-ALP (< upper limit of normal,
ULN)
Proportion of patients with partial normalisation of s-ALP (< 1.5 ULN) · s-ALP
at each study visit (screening to follow-up)
Absolute and relative changes (%) of s-ALP from baseline to each visit up to
EOT, and from EOT to the follow-up visit
*-GT, AST, ALT and serum bilirubin levels at each study visit (screening to
follow-up)
Absolute and relative changes (%) of *-GT, AST, ALT and serum bilirubin from
baseline to each visit up to EOT, and from EOT to the follow-up visit
Course of pruritus (measured by VAS): absolute change in the pruritus score
from baseline to EOT, and from EOT to the follow-up visit
Course of fatigue (measured by questionnaire): absolute change from baseline to
EOT
Therapeutic success and therapeutic benefit according to physician*s global
assessment (PGA) of efficacy at the EOT visit.
Background summary
This double-blind, randomised, placeo-controlled, dose-finding study will be
the proof of concept study and is the third human exposure study with norUDCA
and the first human study to assess efficacy in addition to safety and
tolerability. The present dose finding study should provide first information
on a safe and effective norUDCA dose administered to humans.
Based on the obtained results in this study, the optimal pharmaceutical dose
with regard to clinical outcomes as well as to patient's quality of life will
be chosen, to be evaluated in further phase III confirmative trials.
Study objective
Primary:
* To evalaute 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:
* To study safety and tolerability (adverse events, laboratory parameters) of
norUDCA
* To assess quality of life.
Study design
Double-blind, randomized, placebo-controlled, parallel, explorative phase II
dose-finding study.
Intervention
Double-blind, randomised (1:1:1:1) treatment phase:
Patients will be randmised to be treated during 12 weeks with:
Group A: nor-ursodeocholzuur 500 mg once daily 2x250 mg capsules
Group B: nor-ursodeocholzuur 1000 mg once daily 4x250 mg capsules
Group C: nor-ursodeocholzuur 1500 mg once daily 6x250 mg capsules
Group D: placebo capsules for norUDCA once daily.
Study burden and risks
Physical examination 5x
ECG 2x
Echography of the upper abdomen 2x
Vena puncture 9x
Urine examination 9x
Questionnaires regarding pruritus, general well being and fatigue ake 2x
Completion of a diary (only for patients with concommittant inflammatory bowel
disease)
10 visits in total.
Leinenweberstrasse 5
Freiburg 79108
DE
Leinenweberstrasse 5
Freiburg 79108
DE
Listed location countries
Age
Inclusion criteria
1. Signed informed consent,;2. Male or female patients * 18 and < 80 years,;3. PSC verified by 2 of the following criteria:
* Chronische cholestatic diesease of at least 6 month duration
* Retrograde, operative, percutaneous, or magnestic resonance cholangiography *
* Liver biopsy available for review and compatible with the diagnosis of PSC;
4. Alkaline Phosphatase * 1,5 x ULN at baseline
5. PSC Patients with or without IBD
6. Women of child-bearing potential have to apply during the entire duration of the study a highly effective method of birth control
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 (> 51,3µmol/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 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | EU Clinical Trial Directive |
| EudraCT | EUCTR2011-002754-31-NL |
| CCMO | NL40829.018.12 |