Efficacy and safety of niacin/laropiprant

Study design Multicentre, randomized, double-blind trial in 1,455 dyslipidemic patients. 2-week placebo run-in, 16-week treatment period and 2-week follow-up. ER-niacin/laropiprant (ER-N/L, 12 g/d at 4 weeks) vs. ER-niacin (ER-N, titrating 0.5 g/d every 4 weeks to 2 g/d. This randomized, double-blind trial compared the efficacy and tolerability of two niacin treatment regimens: 1) rapid titration with extended-release niacin (ER-niacin)/laropiprant (12 g/day) or 2 gradual titration with ER-niacin /(starting dose 0.5 g/d, increasing by 0.5 g/d every 4 weeks to a target dose of 2 g/d). Patients completed a 2-week run-in period, a 16-week treatment period and were then followed-up at 2 weeks after the end of treatment. Reference 1. Maccubbin D, Koren MJ, Davidson MH et al. Am J Cardiol 2009;104:74-81. Maccubbin D et al. Am J Cardiol 2009;104:74-81

Study end points Frequency and severity of flushing, assessed by 11-point Global Flushing Severity Scale (GFSS). % Change from baseline in lipids. Adverse events, physical findings, vital signs, laboratory evaluations. The primary study end point was the effect of treatment on flushing as assessed by the number of days per week with moderate, severe or extreme flushing. Flushing was assessed using the Global Flushing Severity Scale (GFSS), an 11-point symptom questionnaire: 0: none 1-3 mild 4-6 moderate 7-9 severe 10 extreme. Reference 1. Maccubbin D, Koren MJ, Davidson MH et al. Am J Cardiol 2009;104:74-81. Maccubbin D et al. Am J Cardiol 2009;104:74-81

Global Flushing Severity Scale 0 None 1-3 Mild 4-6 Moderate 7-9 Severe 10 Extreme Maccubbin D et al. Am J Cardiol 2009;104:74-81

Patient characteristics ER-N/Laropiprant (n=726) ER-N (n=729) Age; yrs 57  12 56  11 Women 42% 43% LDL-C mg/dL 111  40 11139 HDL-C mg/dL 46 13 4714 TG mg/dL 163 159 Statin therapy 48% 46% Maccubbin D et al. Am J Cardiol 2009;104:74-81

Frequency of flushing >2 times as many patients on ER-niacin/laropiprant than ER-niacin had no flushing (47% vs. 22%). Patients on ER-niacin/laropiprant had significantly less flushing than patients on ER-niacin over the 16-week period. Overall, more than twice as many patients had no episodes of moderate, severe or extreme flushing with ER-niacin/laropiprant than ER-niacin (47% vs. 22%). Additionally, treatment with ER-niacin/laropiprant was associated with significantly less severe/extreme flushing (24.4% vs. 50.8%, p<0.001). Reference 1. Maccubbin D, Koren MJ, Davidson MH et al. Am J Cardiol 2009;104:74-81. Maccubbin D et al. Am J Cardiol 2009;104:74-81

Discontinuation due to flushing Fewer patients on ER-N/laropiprant than ER-N discontinued due to flushing (7.4% vs. 12.4%, p=0.002). Maccubbin D et al. Am J Cardiol 2009;104:74-81

% Change in lipids at 16 weeks ER-niacin/laropiprant produced greater % changes in HDL-C and LDL-C than ER-niacin over the 16-week treatment period. Reference 1. Maccubbin D, Koren MJ, Davidson MH et al. Am J Cardiol 2009;104:74-81. Maccubbin D et al. Am J Cardiol 2009;104:74-81

Conclusions ER-niacin/laropiprant (12 g/day over 4 weeks) had an improved flushing profile vs. gradually titrated ER-niacin. These findings support this rapid titration regimen with ER-niacin/laropiprant. Maccubbin D et al. Am J Cardiol 2009;104:74-81