title: Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies).
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.
authors.affiliation: Teikyo Academic Research Center, Tokyo, Japan. Electronic address: ttera@med.teikyo-u.ac.jp.
authors.forename: Tamio
authors.initials: T
authors.lastname: Teramoto
authors.affiliation: Therapeutic Strategy Unit, Asia Pacific R&D, Sanofi, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Primary and Consumer Health Care Medical, Medical Operations, Sanofi, Tokyo, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.affiliation: Biostatistics, Biostatistics and Programming, Clinical Sciences and Operations, R&D, Sanofi, Tokyo, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Heishinkai Medical Group Incorporated ToCROM Clinic, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuoka
authors.affiliation: Koganeibashi Sakura Clinic, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Heishinaki Medical Group Incorporated OCROM Clinic, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Daiwa Hospital, Osaka, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Minami
authors.affiliation: PCSK9 Development and Launch Unit, Sanofi, Montpellier, France.
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Baccara-Dinet
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; C571059:alirocumab