title: Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of inclacumab in healthy Japanese and Caucasian subjects.
abstract: OBJECTIVE
  Inclacumab, a novel monoclonal antibody against P-selectin, is in development for the treatment and prevention of atherosclerotic cardiovascular diseases. This study was conducted to investigate potential differences in the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single intravenous doses of inclacumab between Japanese and Caucasian healthy volunteers.
  
  
  METHODS
  Sixty-two subjects (31 Japanese and 31 Caucasian) were enrolled in a single-center, open-label, parallel, three dose groups (0.3, 3.0, and 20 mg/kg), single-dose study in Japanese and Caucasian healthy volunteers. Inclacumab concentrations, platelet-leukocyte aggregates (PLA), free/total soluble P-selectin (sP-selectin) ratio, and antibody formation were measured along with routine safety monitoring during the conduct of the study.
  
  
  RESULTS
  The PK profiles of inclacumab in Caucasian and Japanese subjects were similar following single-dose intravenous infusion. The statistical analysis of peak (C max) and total exposure (AUClast) indicated that bioavailability was similar for both races when corrected for body weight. The geometric mean ratios for AUClast and C max in the Japanese versus Caucasian cohort were 101 and 111%, respectively, in 0.3 mg/kg dose group, 108 and 107%, respectively, in 3.0 mg/kg dose group, and 97 and 96%, respectively, in 20 mg/kg dose group. No differences were observed in the level of PLA inhibition and mean free/total soluble P-selectin ratio between Japanese and Caucasian subjects. PK/PD relationship between the free/total sP-selectin ratio or PLA and plasma concentration of inclacumab appeared to be similar in both Japanese and Caucasian populations. The effect of race as a covariate was explored on both PK/PD models for PLA and free/total sP-selectin ratio and did not have a significant effect over the reduced model without race as a covariate.
  
  
  CONCLUSIONS
  Ethnicity had no clinically relevant influence on inclacumab pharmacokinetics or pharmacodynamics. No dose adjustment of inclacumab is required for differences in race.
authors.affiliation: Roche Innovation Center Welwyn, Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Morrison
authors.affiliation: Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, CH-4070, Basel, Switzerland.
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Palermo
authors.affiliation: Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, CH-4070, Basel, Switzerland. christophe.schmitt@roche.com.
authors.forename: Christophe
authors.initials: C
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D044466:Asian People; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects; D044465:White People; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D019007:P-Selectin; C546937:SELP protein, human; C000604431:inclacumab
keywords: Caucasian; Ethnicity; Inclacumab; Japanese; Monoclonal antibody; P-selectin; Pharmacodynamics; Pharmacokinetics