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

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 studie...

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Vydáno v:Clinical pharmacology and therapeutics Ročník 103; číslo 5; s. 815
Hlavní autoři: de Hoon, Jan, Van Hecken, Anne, Vandermeulen, Corinne, Yan, Lucy, Smith, Brian, Chen, Jiyun Sunny, Bautista, Edgar, Hamilton, Lisa, Waksman, Javier, Vu, Thuy, Vargas, Gabriel
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.05.2018
Témata:
Adolescent
Adult
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized - therapeutic use
Calcitonin Gene-Related Peptide - metabolism
Calcitonin Gene-Related Peptide Receptor Antagonists - therapeutic use
Double-Blind Method
Female
Healthy Volunteers
Humans
Male
Middle Aged
Migraine Disorders - drug therapy
Migraine Disorders - metabolism
Signal Transduction - drug effects
Young Adult
ISSN:1532-6535, 1532-6535
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Popis
Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1532-6535
1532-6535
DOI:10.1002/cpt.799