Pharmacokinetics/pharmacodynamics by race: Analysis of a peginterferon β-1a phase 1 study.

Autor: Zhao Y; Biogen, Cambridge, MA 02142, USA., Mokliatchouk O; Biogen, Cambridge, MA 02142, USA., Ramia NF; Biogen, Cambridge, MA 02142, USA., Naylor ML; Biogen, Cambridge, MA 02142, USA., Butts CL; Biogen, Cambridge, MA 02142, USA. Electronic address: cherie.butts@biogen.com.
Jazyk: angličtina
Zdroj: Med (New York, N.Y.) [Med] 2022 Sep 09; Vol. 3 (9), pp. 612-621.e3. Date of Electronic Publication: 2022 Jul 18.
DOI: 10.1016/j.medj.2022.06.006
Abstrakt: Background: Black/African American participants are underrepresented in clinical trials for multiple sclerosis but can experience a greater burden of disease than other racial groups in the United States. A phase 1, open-label, crossover study that demonstrated bioequivalence of subcutaneous and intramuscular injection of peginterferon β-1a in healthy volunteers enrolled similar proportions of Black and White participants, enabling a post hoc subgroup analysis comparing these groups.
Methods: Peginterferon β-1a (125 μg) was administered by subcutaneous or intramuscular injection, followed by a washout period before a second injection using the alternative method. The primary pharmacokinetic and pharmacodynamic endpoints were maximum observed concentration (C max ) and area under the concentration-time curve from hour 0 to infinity (AUC inf ) of study drug and serum concentration of neop-terin, respectively. Safety and tolerability were included as secondary endpoints.
Findings: This analysis included 70 (51.5%) Black and 59 (43.3%) White participants. Peginterferon β-1a C max was 29.8% higher in Black than in White participants following subcutaneous administration but was similar following intramuscular administration. Mean AUC inf was 31.0% and 11.8% greater in Black than in White participants with subcutaneous and intramuscular administration, respectively. Pharmacodynamics and safety signals were similar between groups, although Black participants reported numerically fewer adverse events.
Conclusions: No clinically meaningful differences were identified between Black and White participants related to peginterferon β-1a administration, supporting the approved dose of 125 μg/mL peginterferon β-1a. Future clinical studies should include sufficiently diverse populations to ensure accurate assessments of treatment response.
Funding: Funding for medical writing support was provided by Biogen (Cambridge, MA, USA).
Competing Interests: Declaration of interests Y.Z. and M.L.N. were employees of Biogen Inc. at the time of these analyses; O.M., N.F.R., and C.L.B. are employees of Biogen Inc.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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