NAUTILUS (The multiceNtre, open, uncontrolled sAfety and tolerability stUdy of a modified-release nicoTinic acId formuLation in sUbjects with dySlipidaemia and low HDL cholesterol) was an open label, uncontrolled, phase IIIb study. The study population included a total of 566 patients with dyslipidaemia and low high-density lipoprotein (HDL) cholesterol (< 1.0 mmol/L [< 40 mg/dL] in men and < 1.2 mmol/L [< 46 mg/dL] in women) who were inadequately controlled by diet alone. Patients received once-daily treatment with prolonged release nicotinic acid (Niaspan®; target dose 2,000 mg/day), added to existing regimens for 15 weeks. At baseline, 40.5% of patients were receiving an HMG-CoA reductase inhibitor (statin), mostly simvastatin or atorvastatin.
Patients taking and not taking concomitant statin therapy reported a similar incidence of all-cause adverse events (AE) of 64.6% vs. 57.9%, respectively, treatment- related AE (54.6% vs. 47.2%), all-cause serious AE (3.9% vs. 3.6%), treatment-related serious AE (0.9% vs. 0.3%), and withdrawals for AE (17.5% in each group). The incidence of flushing was similar in patients with and without statin treatment (45.0% vs. 40.1%), as was the proportion of patients withdrawing because of flushing (8.7% vs. 10.4%). Only about one quarter of patients flushed more than five times. There was no sign of serious hepatic or muscle toxicity. The addition of prolonged-release nicotinic acid markedly raised HDL cholesterol levels irrespective of statin treatment; it was well tolerated and effective when combined with a statin in patients with dyslipidaemia.