Combination Obeticholic Acid (OCA) and Statins for Monitoring of Lipids (CONTROL)

Inclusion Criteria

• Age ≥18 years
• Histologic evidence of NASH, as assessed by central reading of a liver biopsy obtained no more than 1 year prior to randomization, defined by the presence of all 3 key histological features of NASH with a score of at least 1 for each and a combined score of 4 or greater out of a possible 8 points according to NASH Clinical Research Network (CRN) criteria.
• Histologic evidence of fibrosis stage 1 to stage 4 (as defined by NASH CRN scoring of fibrosis) without any evidence of hepatic decompensation.
• If subject has type 2 diabetes, is on stable dose of anti-diabetic medication (except thiazolidinediones [TZDs]) for ≥3 months prior to Day 1.
• Is either not taking or is on stable doses of TZDs and/or Vitamin E for ≥6 months prior to Day 1.
• Contraception: Female subjects of childbearing potential must use ≥1 effective method of contraception during the study and until 30 days following the last dose of investigational product. Effective methods of contraception are considered to be the following: barrier method, ie, condom (male or female) with spermicide or diaphragm with spermicide, intrauterine device, vasectomy (partner), hormonal (eg, contraceptive pill, patch, intramuscular implant or injection), abstinence (defined as refraining from heterosexual intercourse).
• Must provide written informed consent and agree to comply with the study protocol, including adherence to protocol-described statin withdrawal and statin therapy.

Exclusion Criteria

• Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening Visit 1 (significant alcohol consumption is defined as more than 2 units/day in females and more than 4 units/day in males, on average)
• Prior intolerance to treatment with atorvastatin or other 3-hydroxy-3-methyl-glutaryl (HMG) Coenzyme A reductase inhibitors (including but not limited to rhabdomyolysis).
• LDL cholesterol ≥190 mg/dL and already on statin therapy at Screening Visit 1.
• LDL cholesterol >200 mg/dL at any Screening Visit in subjects who are not on statin therapy, or at Screening Visit 2 in statin washout subjects.
• Planned change in diet or exercise habits during participation in the double-blind period, or a significant weight change of >5% in the prior 6 months.
• Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures.
• History of biliary diversion
• Uncontrolled diabetes defined as HbA1c ≥9.5% within 60 days prior to randomization (Day 1).
• Administration of any of the following medications as specified below:
• Prohibited 30 days prior to Day 1:
• bile acid sequestrants (BAS) including cholestyramine and its derivatives, colesevelam, colestipol, or
• omega-3 fatty acid-containing dietary supplements
• Prohibited 3 months prior to Day 1:
• nicotinic acid and derivatives, ezetimibe
• any prescription or over-the-counter (OTC) medication or herbal remedy with putative NASH efficacy (except Vitamin E or TZDs)
• ursodeoxycholic acid
• fenofibrate or other fibrates
• any OTC or health food used to treat lipids including plant sterols and berberine
• Prohibited 6 months prior to Day 1:
• azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate, mofetil, pentoxifylline; budesonide and other systemic corticosteroids, or
• potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)
• Prohibited 12 months prior to Day 1:
• antibodies or immunotherapy directed against interleukins, or
• other cytokines or chemokines
• Evidence of other forms of chronic liver disease including but not limited to:
• Positive test result at Screening for hepatitis B surface antigen
• Active hepatitis C virus (HCV) infection (positive for HCV ribonucleic acid [RNA] at Screening) or history of positive HCV RNA test result
• Primary biliary c