The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease

Inclusion Criteria

• Age 18-75 at study entry.
• Is male, or female and, if female, meets all of the following criteria:
• Not breastfeeding
• Post-menopausal or negative serum pregnancy test result (human chorionic gonadotropin, beta subunit [β-hCG]) at Screening /Visit 1 (Day-14/Week-2) (not required for hysterectomized females)
• If of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectables, oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or in an established relationship with a vasectomized partner) during the entire duration of the study.
• Has been diagnosed with NAFLD via CT (positive for excess liver fat), ultrasound (positive for excess liver fat), MRI (PDFF showing > 15% liver fat) or via biopsy (showing >33% fat) within the past six months. If diagnosis was between 3 and 6 months prior to Screening, an ultrasound (positive for excess liver fat) is required prior to the Screening /Visit 1 (Day-14/Week-2) MRI.
• Has liver fat (as measured by PDFF via MRI) greater than 15% at Screening/Visit 2 (Day-7/Week-1)
• Has had ALT levels >30 U/L for men, >19 U/L for women measured within 8 weeks of enrollment
• Has an HbA1c equal to or less than 9% at Screening /Visit 1 (Day-14/Week-2)
• Has a BMI between 25kg/m2 and 40 kg/m2
• Otherwise stable health for preceding twelve weeks
• Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either normal or with abnormalities consistent with NAFLD.
• Is able to read, understand, and sign the informed consent forms (ICF) and, when applicable, an authorization to use and disclose protected health information form (consistent with Health Insurance Portability and Accountability Act of 1996 [HIPAA] legislation), communicate with the investigator, and understand and comply with protocol requirements.

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Exclusion Criteria

• Clinically significant renal dysfunction defined as a serum creatinine concentration >1.4 mg/dL (females) or >1.6 mg/dL (males) or a blood urea nitrogen concentration >45 mg/dL at screening.
• Use of any of the following medications:
• Metformin
• Combination drugs that include Metformin
• Sildenafil
• Tadalafil
• Vardenafil
• Pioglitazone
• Rosiglitazone
• Short acting insulins
• An alpha blocker
• Oral nitrates
• Medications associated with increased hepatic steatosis
• Insulins
• OCT2/MATE inhibitors (e.g. cimetidine, quinidine, and pyrimethamine)
• Methotrexate
• Tamoxifen
• Corticosteroids (Nasal steroids are allowed if the subject has been on a stable dose for the past 12 weeks and the dose employed does not exceed the maximal recommended dose.)
• Estrogens
• Amiodarone
• Valproic acid
• Coumadin
• Isoniazide
• Nucleoside analogues used for the treatment of HIV infections
• Any dietary supplement other than multi-vitamins
• Evidence of significant alcohol consumption (defined as >7 drinks/week for females and >14 drinks/week for males) within 6 months prior to randomization or presence or suspicion of other forms of chronic liver disease (e.g., cirrhosis, autoimmune hepatitis (>1:160 ANA), Wilson's disease, Hemochromatosis (Ferritin >1000 ug/L and percent iron saturation >45%), hepatitis A, B or C)
• Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:
• Unable to undergo MRI or contraindications for MRI procedure
• History of cardio- or cerebro-vascular disease event within the previous