E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic fatty liver disease (NAFLD) |
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E.1.1.1 | Medical condition in easily understood language |
Non-alcoholic fatty liver disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029530 |
E.1.2 | Term | Non-alcoholic fatty liver |
E.1.2 | System Organ Class | 100000004871 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of two doses of norursodeoxycholic acid (norUDCA) vs. placebo for the treatment of NAFLD with or without diabetes mellitus type 2
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E.2.2 | Secondary objectives of the trial |
To identify efficacious norUDCA dose for the treatment of NAFLD for further evaluation in phase III |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent, 2. Male or female patients ≥ 18 and < 75years, 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 (estrogen and progestogen), 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.
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E.4 | Principal exclusion criteria |
4. 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) • Primary Sclerosing Cholangitis •Wilson’s Disease • Haemochromatosis • Autoimmune Hepatitis • α1AT deficiency • Known bile duct obstruction • Drug induced liver disease • Suspected or proven liver cancer 5. Treatment with any of the following drugs potentially associated with NAFLD within the last 3 months prior to baseline including amiodarone, glucocorticosteroids, nifedipin, diltiazem, anabolic steroids, valproic acid, methotrexate, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement and contraceptive use, 11. Presence of cirrhosis > Child Pugh Score A, 12. History or presence of hepatic decompensation (e.g. variceal bleeding, INR > 1.3), hepatic encephalopathy or poorly controlled ascites, 15. AST or ALT > 4 x ULN, 16. Any relevant infectious disease (e.g. active tuberculosis, HIV), 17. Abnormal renal function (Cystatin C > 1,15 x ULN) at screening and/or at baseline visit, 20. Any active malignant disease, or history/treatment thereof in the last five years, 21. Known intolerance/hypersensitivity to study drug, or drugs of similar chemical structure or pharmacological profile, 23. Existing or intended pregnancy or breast-feeding,
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E.5 End points |
E.5.1 | Primary end point(s) |
primary endpoint is the change in serum alanine aminotransferase (ALT) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of treatment (after 12 weeks) |
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E.5.2 | Secondary end point(s) |
s-AST, ALT, GGT at each study visit ALT/AST ratio at each study visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of treatment (after 12 weeks), some endpoints additionally at each visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Two diffferent doses of IMP (500 or 1500 mg norursodeoxycholic acid) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 24 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |