The Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis

Inclusion Criteria

• Male between 18 and 80 years of age, inclusive.
• Subject with histologic evidence of NASH upon central read of a liver biopsy.

i. A historical biopsy no more than 4 months before Screening may be considered for use with medical monitor approval if the following criteria are met:

• Stable weights between the time of the biopsy and Screening. Stable weight is defined as no more than a 5% change.
• Is either not taking or is on a stable dose of Thiazolidinedione(TZDs)/glitazones for 3 months before Day 1.
• Background therapy for other ongoing chronic conditions, and weight should be stable for at least 3 months before trial enrollment. Stable weight is defined as no more than a 5% change.
• Judged to be in good general health as determined by the investigator at screening.

Exclusion Criteria

• Significant alcohol consumption more than 30 g/day on average, either currently or for a period of more than 3 consecutive months in the 5 years prior to screening.
• Inability to reliably quantify alcohol intake.
• Biochemical, clinical or histologic evidence of cirrhosis on liver biopsy (stage 4 fibrosis).
• Evidence of other causes of chronic liver disease including alcoholic liver disease, viral hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, human immunodeficiency virus, etc.
• Suspected or proven liver cancer.
• Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to:
• Hematocrit > upper limits of normal (ULN)
• Hemoglobin > ULN
• Prostate-specific antigen (PSA) > 4 ng/mL
• Serum aspartate aminotransferase (AST) or alanine transaminase (ALT) > 200 IU/L
• Serum alkaline phosphatase (ALP) > 2 x ULN
• Serum creatinine of 2.0 mg/dL or greater
• Total bilirubin > ULN
• International normalized ratio (INR) ≥ 1.3.
• Prolactin > ULN
• Subjects with evidence of worsening liver function based on the two initial laboratory values used to establish the screening / baseline values.
• Model for End-Stage Liver Disease (MELD) score greater than 12
• Subjects with a documented history of Gilbert's syndrome
• Evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly).
• Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens, anabolic steroids, valproic acid, other known hepatotoxins) for more than 2 weeks in the 2 years prior to randomization.
• Subjects who are not on a stable dose of lipid-lowering drugs, diabetic and / or hypertensive medication in the 3 months prior to biopsy or the 3 months prior to randomization
• Any over-the-counter medication or herbal remedy that is being taken with an intent to improve hyperlipidemia must be stable for at least 3 months prior to randomization and through the end of the study.
• Vitamin E supplementation of greater than 100 IU/day, unless completed adequate washout for at least 4 weeks prior to Day 1 or biopsy if one is required.
• Inability to safely obtain a liver biopsy.
• History of total parenteral nutrition in the year prior to screening.
• History of bariatric surgery or currently undergoing evaluation for bariatric surgery.
• History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.
• History of biliary diversion.
• Known positivity for antibody to Human Immunodeficiency Virus (HIV).
• Known heart failure of New York Heart Association class 3 or 4.
• Active, serious medical disease with likely life-expectancy less than 5 years.
• History of current or suspected prostate or breast cancer.
• History of diagnosed, severe, untreated, obstructive sleep apnea.
• Active s