A Phase I Randomized Study of a Specifically Engineered, pH‐Sensitive PCSK9 Inhibitor RN317 (PF‐05335810) in Hypercholesterolemic Subjects on Statin Therapy
| Autor: | Levisetti, M, Joh, T, Wan, H, Liang, H, Forgues, P, Gumbiner, B, Garzone, PD |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Dose-Response Relationship Drug Research Injections Subcutaneous Hypercholesterolemia PCSK9 Inhibitors Antibodies Monoclonal Cholesterol LDL Hydrogen-Ion Concentration Middle Aged Antibodies Monoclonal Humanized Protein Engineering Phase Forward Injections Intravenous Humans Drug Therapy Combination Female Hydroxymethylglutaryl-CoA Reductase Inhibitors Proprotein Convertase 9 Demography |
| Zdroj: | Clinical and Translational Science |
| ISSN: | 1752-8062 1752-8054 |
| Popis: | This phase I study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of RN317 (PF-05335810), a specifically engineered, pH-sensitive, humanized proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibody, in hypercholesterolemic subjects (low-density lipoprotein cholesterol (LDL-C) ≥ 80 mg/dl) 18-70 years old receiving statin therapy. Subjects were randomized to: single-dose placebo, RN317 (subcutaneous (s.c.) 0.3, 1, 3, 6, or intravenous (i.v.) 1, 3, 6 mg/kg), or bococizumab (s.c. 1, 3, or i.v. 1 mg/kg); or multiple-dose RN317 (s.c. 300 mg every 28 days; three doses). Of 133 subjects randomized, 127 completed the study. RN317 demonstrated a longer half-life, greater exposure, and increased bioavailability vs. bococizumab. RN317 was well tolerated, with no subjects discontinuing because of treatment-related adverse events. RN317 lowered LDL-C by up to 52.5% (day 15) following a single s.c. dose of 3.0 mg/kg vs. a maximum of 70% with single-dose bococizumab s.c. 3.0 mg/kg. Multiple dosing of RN317 produced LDL-C reductions of ∼50%, sustained over an 85-day dosing interval. |
| Databáze: | OpenAIRE |
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