A placebo-controlled clinical trial to evaluate the efficacy and safety of two Aramchol doses in patients with Non-Alcoholic- Steatohepatitis (NASH).

• Conditions: on-alcoholic Steatohepatitis in patients with two additional features of metabolic syndrome -overweight or obesity and Diabetes Mellitus type II or pre-diabetes.; MedDRA version: 18.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-003107-29-RO
• Lead Sponsor: GALMED Pharmaceuticals LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-10-07
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Male or female age 18 to 75 years,
2.25 = BMI =40 kg/m2 or waist circumference > 88 <200 cm for women and > 102 <200 cm for men.
3.Known type II Diabetes Mellitus or pre-Diabetes according to American Diabetes Association (one of three needed): Fasting Plasma Glucose > 100mg/dl (5.5 mmole/l) or 2hPG following 75g OGTT > 140 (7.8 mmole/l) mg/dl or HbA1C > 5.7%.
4.Histologically proven Steatohepatitis on a diagnostic liver biopsy performed within 6 months before randomization, confirmed by central laboratory reading of the slides (steatosis > 5%+ lobular inflammation, any ballooning, any amount).
5.Fat concentration in the liver of 5.5% or more as measured by NMRS.
6.Biopsies with an activity NAS score of 4 or more.
7.Normal synthetic liver function (serum albumin >3.5g/l, INR 0.8-1.3).
8.Signature of the written informed consent.
9.Negative pregnancy test at study entry for females of child bearing potential.
10.Females of child bearing potential practicing reliable contraception throughout the study period (including oral contraceptives).
11.Hypertensive patients must be well controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
12.Patients previously treated with vitamin E (>400IU/day), Polyunsaturated fatty acid (>2g/day) or Ursodeoxycholic acid or fish oil can be included if drugs are stopped at least 3 months prior to diagnostic liver biopsy and up to the end of study.
13.For patients with type II Diabetes, glycaemia must be controlled (Glycosylated Hemoglobin A1C = 9% while any HbA1C increment should not exceed 1% during 6 month prior to enrollment). Treatments with Metformin, Sulfamides and Insulin are authorized. Sulfamides and insulin are permitted if glycaemia is self-monitored by the patient.

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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.Patients with other active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, genetic hemochromatosis, Wilson disease, alpha 1antitripsin deficiency, alcohol liver disease, drug induces liver disease) at the time of randomization.
2.Patients who have liver cirrhosis.
3.Known Alcohol and/or any other drug abuse or dependence in the last five years.
4.Known history or presence of clinically significant cardiovascular, hepatic other than NASH, gastrointestinal, metabolic other than Diabetes Mellitus, neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephrotic syndrome.
5.History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including bile salt metabolism (e.g. inflammatory bowel disease (IDB); previous intestinal (ileal or colonic) operation; chronic pancreatic; celiac disease or previous vagotomy.
6.Patients with heart or brain pacemaker
7.History of surgery during the last three month before screening which involved stent transplant or any other surgery which includes transplantation of metal devices (e.g. knee, hip etc.)
8.Weight loss of more than 5% within 6 months prior to randomization.
9.History of bariatric surgery in the past 5 years to liver biopsy.
10.Uncontrolled blood pressure.
11.Diabetes Mellitus other than type II (type I, endocrinopathy, genetic syndromes etc.).
12.Patients with HIV infection.
13.Daily alcohol intake >20 g/day for women and 30 g/day for men.
14.Treatment with other anti-diabetic medications: DPP-4 inhibitors and GLP-1 receptor agonists (such as Genuvia, Sitagliptin, Byetta [Incretin], etc.)
15.Metformin, Fibrates, Statins, Insulin, Sulfonylurea unless dose has been stabilized over the last 6 months.
16.Patients who are treated with Valproic acid, Tamoxifen, Methotraxete, Amiodaron.
17.Chronic antibiotic treatment (e.g. Rifaximin).
18.Homeopathic and/or Alternative treatments. Any treatment should be stopped before the screening period.
19.Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone >2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
20.Patients with renal dysfunction eGFR< 40.
21.Unexplained serum creatine phosphokinase (CPK) >3X the upper limit of normal (ULN). Patients with an intermittent CPK elevation may have the repeated measurement prior to randomization; a CPK retest > 3X ULN leads to exclusion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified