Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine

被引：66

作者：

de Hoon, Jan ^{[1
]}

Van Hecken, Anne ^{[1
]}

Vandermeulen, Corinne ^{[1
]}

Yan, Lucy ^{[2
]}

Smith, Brian ^{[2
]}

Chen, Jiyun Sunny ^{[2
]}

Bautista, Edgar ^{[2
]}

Hamilton, Lisa ^{[3
]}

Waksman, Javier ^{[4
]}

Thuy Vu ^{[2
]}

Vargas, Gabriel ^{[2
]}

机构：

[1] Univ Hosp Leuven, Ctr Clin Pharmacol, Leuven, Belgium

[2] Amgen Inc, Early Dev, Thousand Oaks, CA USA

[3] Amgen Ltd, Global Biostat, Uxbridge, Middx, England

[4] Amgen Inc, Global Safety, Thousand Oaks, CA USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2018年 / 103卷 / 05期

关键词：

GENE-RELATED PEPTIDE; CGRP RECEPTOR ANTAGONIST; DERMAL BLOOD-FLOW; MONOCLONAL-ANTIBODY; INDUCED VASODILATION; CONTROLLED-TRIAL; PREVENTION; TELCAGEPANT; SAFETY; PREVALENCE;

D O I：

10.1002/cpt.799

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase I studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin G2 antibodies. Single doses of erenumab resulted in >75% inhibition of capsaicin-induced dermal blood flow, with no apparent dose-dependency for erenumab 21 mg. Erenumab was generally well tolerated, with an acceptable safety profile, supporting further clinical development of erenumab for migraine prevention.

引用

页码：815 / 825

页数：11

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