Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies) - 17/06/16
Abstract |
We assessed the safety and tolerability of ascending single doses of alirocumab in healthy Japanese subjects and evaluated the effect of alirocumab at 3 doses (50, 75, 150 mg) on low-density lipoprotein cholesterol (LDL-C) reduction in patients with primary hypercholesterolemia on atorvastatin. A randomized, single ascending-dose study of alirocumab (100, 150, 250, or 300 mg) or placebo (3:1 ratio), administered subcutaneously, was conducted in 32 healthy Japanese men. The phase 2, randomized, double-blind, placebo-controlled, parallel-group study was performed in patients with primary hypercholesterolemia (defined as calculated LDL-C ≥100 mg/dl [2.6 mmol/l]) who were on a stable dose of atorvastatin (5 to 20 mg). Patients were randomized to alirocumab (50, 75, or 150 mg) or placebo (in single 1.0-ml injection volumes) administered every 2 weeks (Q2W) for 12 weeks; the primary outcome was the mean percent change in calculated LDL-C from baseline to week 12. Single subcutaneous administration of alirocumab in healthy subjects was well tolerated over 15 weeks and resulted in highest mean percent reductions in LDL-C from baseline of approximately 40% to 60%. In the multiple-dose study, least-square mean (SE) changes in calculated LDL-C concentrations from baseline to week 12 were −54.8% (3.1%) for alirocumab 50 mg, −62.3% (3.1%) for alirocumab 75 mg, and −71.7% (3.1%) for alirocumab 150 mg, with a least-square mean (SE) difference versus placebo of −52.2% (4.3%), −59.6% (4.3%), and −69.1% (4.3%), respectively (all p <0.0001). In conclusion, alirocumab was well tolerated and significantly reduced LDL-C concentrations in Japanese patients with primary hypercholesterolemia on atorvastatin.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Alirocumab reduced low-density lipoprotein cholesterol (LDL-C) in Japanese healthy male subjects. |
• | Alirocumab reduced LDL-C by 54.8% to 71.7% in patients with hypercholesterolemia. |
• | No safety or tolerability concerns were apparent with alirocumab. |
Plan
Funding Sources: This study is funded by Sanofi, USA, and Regeneron Pharmaceuticals, Inc., USA. |
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ClinicalTrials.gov numbers: NCT01448317 (phase 1) and NCT01812707 (phase 2). |
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See page 62 for disclosure information. |
Vol 118 - N° 1
P. 56-63 - juillet 2016 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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