A Clinical Trial to Evaluate the Efficacy and Safety of Two Aramchol Doses Versus Placebo in Patients With NASH (Aramcho

Description

This is a multicenter, Phase IIb, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects that are 18 to 75 years of age, with Non-Alcoholic Steatohepatitis (NASH) confirmed by liver biopsy performed in a period of 6 months before entering the study, with overweight or obesity and who are pre diabetic or type II diabetic. Eligible subjects will be enrolled into three treatments arms: Aramchol 400 and 600 mg tablets and placebo tablets in ratio 2:2:1. The subjects will be evaluated at study sites for 11 scheduled visits during one year (52 weeks). After completion of the study treatment period, the subjects will be followed for an additional period of 13 weeks without study medication (until visit 11 (week 65)).

Study Start Date

January 2015

Estimated Completion Date

June 2017

Interventions

  • Drug: Aramchol

Specialties

  • Infectious Disease: Hepatitis
  • Gastroenterology: Hepatology
  • Endocrinology: Diabetes
  • Pharmacy: Drug Trials,Stomach/GI

MeSH Terms

  • Digestive System Diseases
  • Fatty Liver
  • Liver Diseases

Study ID

Galmed Pharmaceuticals Ltd -- 005

Status

Unknown

Trial ID

NCT02279524

Study Type

Interventional

Trial Phase

Phase 2/Phase 3

Enrollment Quota

240

Sponsor

Galmed Pharmaceuticals Ltd

Inclusion Criteria

    1. Male or female age 18 to 75 years. 2. 25 ? BMI ?40 kg/m2 or waist circumference > 88 for women and > 102 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 or 2hPG following 75g OGTT > 140 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 >3.5gm%, 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.

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. Known Alcohol and/or any other drug abuse or dependence in the last five years. 3. 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. 4. 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. 5. Weight loss of more than 5% within 6 months prior to randomization. 6. History of bariatric surgery. 7. Uncontrolled blood pressure. 8. Non type II Diabetes Mellitus (type I, endocrinopathy, genetic syndromes etc.). 9. Patients with HIV. 10. Daily alcohol intake >20 g/day for women and 30 g/day for men. 11. Treatment with other anti-diabetic medications: DPP-4 inhibitors and GLP-1 receptor agonists (such as Genuvia, Sitagliptin, Byetta [Incretin], etc.) 12. Metformin, Fibrates, Statins, Insulin, Sulfonilurea not provided on a stable dose in the last 6 months. 13. Patients who are treated with Valproic acid, Tamoxifen, Methotraxete, Amiodaron. 14. Chronic antibiotic treatment (e.g. Rifaximin). 15. Homeopathic and/or Alternative treatments. Any treatment should be stopped before the screening period. 16. 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. 17. Patients with renal dysfunction eGFR< 40. 18. 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.

Gender

Both

Ages

18 Years to 75 Years

Accepts Healthy Volunteers

No

Study Locations and Contact Information (12)

Study Location Distance Name Phone Email
New York Medical College - New York, New York 29.6 miles Ed Lebovics Dr None None
Mount Sinai - New York, New York 46.8 miles Charissa Chang Dr None None
University of Virginia Medical Center - Charlottesville, Virginia 357.0 miles Stephen Caldwell Prof None None
Wake Research - Raleigh, North Carolina 474.0 miles Charles Barish Dr None None
Duke University Medical Center - Durham, North Carolina 474.7 miles Manal AbdelmaleK Prof None None
Indiana University - Indianapolis, Indiana 686.4 miles Samer Gawrieh Dr None None
San Antonio Military Medical Center - Fort Sam Houston, Texas 1,634.2 miles Stephen A Harrison Prof None None
Texas Liver Institute San Antonio - San Antonio, Texas 1,634.2 miles Fred Poordad Dr None None
Clinical Trials of Texas - San Antonio, Texas 1,635.9 miles Douglas Denham Dr None None
Profile Institue for Clinical Research Inc - Chula Vista, California 2,470.8 miles Elaine Watkins Dr None None
University of California Department of Medicine Division of Gastroenterology - San Diego, California 2,472.6 miles Rohit Loomba Prof None None
Orange County Research Center - Tustin, California 2,476.5 miles Joel M Neutel Dr None None

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