A phase 1 study to assess the pharmacokinetics, safety, and tolerability of fremanezumab doses (225？mg, 675？mg and 900？mg) in Japanese and Caucasian healthy subjects

The primary and secondary objectives of this phase 1 study were to evaluate the pharmacokinetic profile, safety, and immunogenicity of fremanezumab subcutaneous (sc) doses tested in phase 2 and 3 trials (225？mg, 675？mg and 900？mg) following single administration in Japanese (n？=？32) and Caucasian (n？=？32) healthy subjects. Japanese and matched Caucasian healthy subjects were enrolled into one of four cohorts and were randomly assigned to one of four treatments: 225, 675, or 900？mg fremanezumab, or placebo. Pharmacokinetic and immunogenicity sampling, and safety and tolerability assessments occurred at one inpatient visit and 12 ambulatory visits during the 36-week study. Pharmacokinetic analyses included those randomized to fremanezumab (n？=？24 for each ethnic group) and safety analyses included all subjects enrolled in the study (n？=？32 for each ethnic group). Fremanezumab concentration-time profiles and pharmacokinetic parameters per dose were similar for Japanese and Caucasians at all dose levels. Geometric mean ratios (GMRs) for Cmax for Japanese to Caucasian subjects were 0.91, 1.04 and 1.14 for the 225？mg, 675？mg and 900？mg fremanezumab doses. GMRs for AUC0-inf were 0.96, 1.09, and 0.98, respectively. Median Tmax (range 5–11 days) and mean half-lives (range 31–39 days) were similar across doses for both ethnicities. Most frequently occurring adverse events were injection site reactions, abdominal pain, headache, upper respiratory tract infection, constipation and nasopharyngitis. There was no development of anti-drug-antibodies and no clinically meaningful changes in laboratory findings. The results of the pharmacokinetic exposure parameters and safety measures were similar for Japanese and Caucasians and support the once monthly and once quarterly sc injections of fremanezumab