Population Pharmacokinetics of Fasinumab in Healthy Volunteers and Patients With Pain Due to Osteoarthritis of the Knee or Hip.

Autor: Lin KJ; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA., Turner KC; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA., Hassan HE; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA., Harnisch LO; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA., Davis JD; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA., DiCioccio AT; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2024 Jun; Vol. 13 (6), pp. 621-630. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1002/cpdd.1380
Abstrakt: Osteoarthritis (OA) pain management options are currently limited. Fasinumab, an anti-nerve growth factor monoclonal antibody, has been investigated in healthy volunteers and patients with OA-related pain, among other conditions. Data from 12 Phase I-III clinical trials of 92 healthy volunteers and 7430 patients with OA were used to develop a population pharmacokinetic model to characterize fasinumab concentration-time profiles and assess the covariates' effect on fasinumab pharmacokinetic parameters. Participants received single or repeated fasinumab doses intravenously (IV)/subcutaneously (SC), based on body weight (0.03-1 mg/kg IV or 0.1-0.3 mg/kg SC)/fixed dose (9-12 mg IV or 1-12 mg SC). Fasinumab concentration-time data following IV and SC administration in healthy volunteers and patients with OA-related pain were adequately described by a 2-compartment model. Bioavailability increased with higher doses; estimated at 55.1% with 1 mg SC dose, increasing in a greater-than-proportional manner above this. Body weight had the largest predicted impact on fasinumab steady-state exposures, participants at the 5th and 95th percentiles had a 43%-45% higher/22%-23% lower exposure versus reference, respectively. Other covariates had small but clinically irrelevant impacts.
(© 2024 Regeneron Pharmaceuticals, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
Databáze: MEDLINE
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