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CONTROL Trial shows Statin Therapy Reversed LDL increases to below baseline levels in NASH patients treated with OCA
Announced results from CONTROL, a placebo-controlled trial to prospectively characterize the lipid metabolic effects of obeticholic acid (OCA) and concomitant statin administration in patients with nonalcoholic steatohepatitis (NASH) with fibrosis or cirrhosis. The CONTROL trial met its primary objective by showing that newly initiated treatment with atorvastatin rapidly reversed OCA-associated increases in LDL to below baseline levels. Most of the effect was observed four weeks after initiation of the lowest available dose of atorvastatin and was sustained throughout the study period.
CONTROL is a 16-week double-blind, placebo-controlled, dose-ranging study of 84 NASH patients with fibrosis and compensated cirrhosis, followed by a two-year long term safety extension (LTSE) open label phase which is currently ongoing. Lipid changes were assessed every four weeks over the course of the double-blind phase. Details of the study design are as follows:
* Statin-naïve or washout patients were randomized to receive one of three doses of OCA (5 mg, 10 mg or 25 mg) or placebo.
* At week four, the lowest approved dose of atorvastatin (10 mg) was added in all patients.
* At week eight, patients were titrated to the next highest prescribed dose of atorvastatin (20 mg).
* At week 12, further titration of atorvastatin (up to 40 mg) was permitted at investigators’ discretion.
The study was designed to measure treatment differences within each group relative to baseline. The intent-to-treat (ITT) analysis is shown below and includes all patients who received at least one dose of study medication.
At week four, mean LDL levels increased in each of the OCA treatment groups, while remaining relatively unchanged in the placebo group. The addition of 10 mg of atorvastatin rapidly reversed mean LDL to below baseline levels in all OCA treatment groups at the first assessed time point (week eight), and this effect was sustained through week 16. The observed mean LDL reductions in the OCA groups were approximately 40 – 45 mg/dL while placebo was 48 mg/dL.

