E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic steatohepatitis (NASH) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | non-alcoholic steatohepatitis |
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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 assess whether the antibiotic, Rifaximin, reduces liver inflammation in non-alcoholic steatohepatitis (NASH). |
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E.2.2 | Secondary objectives of the trial |
To determine whether Rifaximin's effect on bowel flora leads to: 1. Reduction in liver fat 2. Change in resistance to the energy storage hormone, insulin 3. Change in mediators of inflammation (cytokines)
To determine how changes in the gut bacteria related to the measures stated above. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject has provided written informed consent prior to screening • Men and women aged 18-70 years • Biopsy-proven NASH with no or mild to moderate fibrosis in the preceding year • Persistently abnormal ALT on 2 occasions
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E.4 | Principal exclusion criteria |
• NAFLD with cirrhosis (fibrosis score 4) • Other causes of chronic liver disease o Viral hepatitis (HBV, HCV negative) o Alcohol intake >14units/week (women) or >21units/week (men) o Haemachromatosis (abnormal transferrin saturation, haemochromatosis genotyping) • Evidence of hepatic decompensation o Ascites o Hepatic encephalopathy o Abnormal total bilirubin (except patients with Gilbert’s syndrome), albumin, prolonged prothrombin time, low platelets) o Oesophageal or gastric varices • Moderate or severe renal dysfunction (CKD3+, estimated GFR <60ml/min/1.73m2) • Hepatocellular carcinoma • Primary metabolic causes of hepatic steatosis (e.g. familial hypertriglyceridaemia, abetalipoproteinaemia) • Other malignancy • Pregnant or lactating women or women of childbearing potential unwilling/unable to use adequate contraceptive methods • Systemic inflammatory conditions o Arthritis o Connective tissue disorders o Inflammatory bowel disease • Myocardial infarction within 6 months • Stroke within 6 months • Bariatric surgery/ blind loop/ short bowel • Treatment known/suspected to change gut flora (e.g. systemic antibiotics, colestyramine, lactulose, polyethylene glycol) within 3 months • Treatment with drugs known to cause hepatic steatosis (e.g. corticosteroids, HAART, amiodarone, high dose oestrogens, tamoxifen) within 3 months • Initiation or major dose change of metformin, thiazolinediones, biguanides, statins, fibrates, anti-obesity medications or insulin within 3 months of enrolment • Patients with allergy to Rifaximin or Rifamycin • Patients with a cardiac pacemaker, history of penetrating eye injury, metal foreign body or any other contra-indication to MRI scanning, as specified in the local MRI safety checklist • Any other clinical, social or psychological issues which, in the opinion of the investigators may preclude satisfactory completion of the study protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
The change in serum alanine aminotransferase level after treatment with Rifaximin. |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Demonstration of physiological mechanisms |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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End of 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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |