E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fatty liver disease, morbid obesity, gallstone disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 10019805 - Hepatobiliary disorders |
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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 |
Main trial objectives are to determine whether (i) INT-747 (25 mg/day) improves insulin resistance in patients with non-alcoholic fatty liver disease (NAFLD) (iii) INT-747 alters hepatic and/or white adipose tissue (WAT) lipase activity and fatty acid/triglyceride (FA/TG) content in NAFLD (iv) INT-747 improves hepatobiliary transporter expression in NAFLD and gallstone disease (v) INT-747 improves biliary lipid profiles towards lower cholesterol saturation
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E.2.2 | Secondary objectives of the trial |
Secondary trial objectives are to determine whether (i) INT-747 changes in serum cholesterol and triglycerides (ii) INT-747 changes in energy consumption |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 20 to 65 years; in the obesity group: BMI ≥35 kg/m2 in the gallstone group: symptomatic, ultrasound verified gallstone disease Sex Males, pre-, and post-menopausal females Diagnosis Patients eligible to laparoscopic bariatric and gallstone surgery, respectively Consent Patients should have given their written consent to participate in this study
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E.4 | Principal exclusion criteria |
Chronic liver disease other than NAFLD (viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease)
Previous gastric or small bowel surgery
Inflammatory bowel disease
Uncontrolled diabetes mellitus (fasting blood glucose >6.7 mmol/L), hypothyroidism or hyperthyroidism, or other significant endocrine disease (a subject who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the TSH is within normal range).
Other serious disease, including depressive disorders treated by medication
Patients who will not comply with the protocol.
Pregnancy. Women in childbearing age must adhere to secure anticonception
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E.5 End points |
E.5.1 | Primary end point(s) |
- relative changes in markers for insulin resistance - relative changes in FA and TG - relative changes in hepatic and adipose tissue lipase expression and activity - relative changes in hepatic apical transport proteins ABCG5/8, BSEP, MDR3, MRP2 - relative changes in hepatic ER stress markers
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | Information not present in EudraCT |
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 | No |
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.8.5 | 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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The End-of-Study Visit will take place six month after the surgical intervention. In this visit the possible occurrence of adverse events will be monitored and recorded in the appropriate section of the Case Report Form. The trial will be terminated after 40 patients, 20 with active treatment and 20 serving as controls, from which a complete set of serum, bile, urine, and liver biopsy material is available. |
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |