Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of inclacumab in healthy Japanese and Caucasian subjects.
Purpose: 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 (...
| Published in: | European Journal of Clinical Pharmacology Vol. 71; no. 11; pp. 1365 - 1375 |
|---|---|
| Main Authors: | , , |
| Format: | equations & formulas research tables/charts Journal Article |
| Published: |
Springer Nature
Nov2015
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110465311&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110465311 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Nov2015 vid: 71 iid: 11 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 110465311 110465311 110465311 10.1007/s00228-015-1938-4 NLM26363899 110465311 ppf: 1365 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of inclacumab in healthy Japanese and Caucasian subjects. aug: au: Morrison, Mary Palermo, Guiseppe Schmitt, Christophe affil: Roche Innovation Center Welwyn, Roche Products Ltd, Welwyn Garden City UK sug: subj: Antibodies, Monoclonal Pharmacodynamics Antibodies, Monoclonal Metabolism Japanese Persons White Persons Human Male Female Japan Ethnic Groups Administration, Intravenous Antibodies, Monoclonal Administration and Dosage Biological Availability Race Factors Male Female ab: Purpose: 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. Method: 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) and total exposure (AUC) indicated that bioavailability was similar for both races when corrected for body weight. The geometric mean ratios for AUC and C 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. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|