The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease
Condition: NAFLD
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Leu-Met-Sil 0.5; Leu-Met-Sil 1.0; Placebo
Intervention description: NS-0200 low dose; NS-200 high dose; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The goal of this study is to determine if NS-0200 can reduce the amount of liver fat in
      patients diagnosed with non-alcoholic fatty liver disease (NAFLD). This study will compare
      two doses of NS-0200 to placebo in NAFLD patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-75 at study entry.

          2. Is male, or female and, if female, meets all of the following criteria:

               1. Not breastfeeding

               2. 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)

               3. 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.

          3. 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.

          4. Has liver fat (as measured by PDFF via MRI) greater than 15% at Screening/Visit 2
             (Day-7/Week-1)

          5. Has had ALT levels >30 U/L for men, >19 U/L for women measured within 8 weeks of
             enrollment

          6. Has an HbA1c equal to or less than 9% at Screening /Visit 1 (Day-14/Week-2)

          7. Has a BMI between 25kg/m2 and 40 kg/m2

          8. Otherwise stable health for preceding twelve weeks

          9. Clinical laboratory tests (hematology, clinical chemistry, and urinalysis) either
             normal or with abnormalities consistent with NAFLD.

         10. 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:

          1. 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.

          2. Use of any of the following medications:

               1. Metformin

               2. Combination drugs that include Metformin

               3. Sildenafil

               4. Tadalafil

               5. Vardenafil

               6. Pioglitazone

               7. Rosiglitazone

               8. Short acting insulins

               9. An alpha blocker

              10. Oral nitrates

              11. Medications associated with increased hepatic steatosis

              12. Insulins

              13. 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

              14. Any dietary supplement other than multi-vitamins

          3. 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)

          4. 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:

               1. Unable to undergo MRI or contraindications for MRI procedure

               2. History of cardio- or cerebro-vascular disease event within the previous 6 months

               3. Requires anti-coagulation therapy

               4. Gastrointestinal disorders including, but not limited to, the following:
                  pancreatitis, inflammatory bowel disease, or other diseases associated with
                  malabsorption or persistent abdominal discomfort

               5. Endocrine disorders other than type 2 diabetes and hypothyroidism on stable
                  replacement therapy

               6. Chronic infection (e.g., tuberculosis, human immunodeficiency virus infection,
                  hepatitis A virus, hepatitis B virus, or hepatitis C virus)

               7. Neurological or psychiatric diseases that preclude valid execution of informed
                  consent or may interfere with the subject's compliance with study procedures
                  (e.g., major depressive disorder within the last 2 years, a history of suicidal
                  behavior in the last 3 months)

               8. History of other psychiatric disorders including schizophrenia and bipolar
                  disorder)

          5. Participation in a weight loss program within the past 3 months.

          6. Weight change ≥5% during the past month.

          7. History of substance abuse (including alcohol abuse as defined above) in the past 3
             months or a positive screen for drugs of abuse or alcohol at screening.

          8. Has received any investigational drug within 3 months of Screening.

          9. Has donated blood within 3 months before Screening or is planning to donate blood
             during the study.

         10. Has had a serious infection, such as pneumonia in the previous 12 weeks

         11. Has known allergies or hypersensitivity to metformin, sildenafil or leucine

         12. Is an immediate family member (spouse, parent, child, or sibling; biological or
             legally adopted) of personnel directly affiliated with the study at the clinical study
             site, or NuSirt Biopharma.

         13. Is employed by NuSirt Biopharma (defined as an employee, temporary contract worker, or
             designee responsible for the conduct of the study).

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