Safety, tolerability, pharmacokinetics, and pharmacodynamics of galcanezumab, a monoclonal antibody to calcitonin gene-related peptide, in Healthy Japanese and Caucasian Subjects

Abstract

Galcanezumab, a humanized monoclonal calcitonin gene-related peptide(CGRP)antibody, is being developed for cluster headache and migraine prevention. This study evaluated galcanezumab safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy Japanese and Caucasian subjects. Galcanezumab or placebo was administered as subcutaneous injections to 4 singledose cohorts(5, 50, 120, 300 mg)and 1 multiple-dose cohort(3 consecutive, 300-mg doses, every 4 weeks). Safety measurements included treatment-emergent adverse events (TEAEs), vItal signs, electrocardiograms, clinical laboratory tests, and antidrug antibodies(ADA). Blood samples were analyzed for serum galcanezumab and plasma CGRP concentrations. Twenty-five Japanese and twenty Caucasians, 22 to 63 years of age, were enrolled ; 27 received a single dose(N=6 to 8 per dose level), 8 received multiple doses, and 10 received placebo (8 single dose, 2 multiple dose). Forty-one subjects completed the study (24 single dose, 7 multiple dose, 10 placebo). Galcanezumab was well tolerated in Japanese and Caucasian subjects. There were no apparent dose-related increases in TEAEs or changes in vItal signs, electrocardiogram parameters, laboratory values, or treatment-emergent ADA. Following single and multiple doses, maximum galcanezumab concentrations were observed approximately 5 to 9 days postdose and mean half-life was about 3 to 4 weeks. Increases in area under the concentration-time curve and maximum observed concentration were dose proportional. Galcanezumab pharmacokinetics and pharmacodynamics were similar between Japanese and Caucasian subjects. Plasma CGRP concentrations increased following galcanezumab administration consistent with CGRP (target) binding to galcanezumab(antibody). These data support further development of galcanezumab in Japanese patients.