Pharmacokinetics, pharmacodynamics, and safety of single-dose subcutaneous sarilumab with or without methotrexate in Japanese patients with rheumatoid arthritis : Two single-dose studies
© Japan College of Rheumatology 2022. Published by Oxford University Press..
OBJECTIVES: To assess the safety and pharmacokinetics (PK) of single-dose subcutaneous (SC) sarilumab or tocilizumab SC ± methotrexate (MTX) and to assess the pharmacodynamics (PD) of sarilumab SC or tocilizumab SC monotherapy in Japanese rheumatoid arthritis (RA) patients.
METHODS: TDU13402 was a randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study (NCT01850680). Twenty-four patients (6 per treatment group) received sarilumab 50, 100, or 200 mg plus MTX or placebo (2 per cohort) on Day (D) 1; PK and safety were assessed through D57. PDY14191 was a randomized, open-label, single-dose study (NCT02404558). Thirty patients (15 per arm) received sarilumab 150 mg or tocilizumab 162 mg on D1; PK, PD, and safety were assessed through D43.
RESULTS: TDU13402: mean serum sarilumab exposure increased in a greater than dose proportional manner from 50 to 200 mg dose with no clinically meaningful increase in treatment-emergent adverse events (TEAEs). PDY14191: PK profiles of single-dose sarilumab 150 mg or tocilizumab 162 mg were similar; some numerical differences in PD profiles and TEAEs were observed. Neutrophil count decrease/neutropenia was the most frequently reported TEAE with sarilumab treatment in both studies.
CONCLUSIONS: PK, PD, and safety profiles of single-dose sarilumab SC with/without MTX were consistent with results anticipated in Japanese patients with RA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Modern rheumatology - 33(2023), 2 vom: 02. März, Seite 279-291 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ishii, Tomonori [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.03.2023 Date Revised 06.03.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/mr/roac036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339749687 |
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| 100 | 1 | |a Ishii, Tomonori |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics, pharmacodynamics, and safety of single-dose subcutaneous sarilumab with or without methotrexate in Japanese patients with rheumatoid arthritis |b Two single-dose studies |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Japan College of Rheumatology 2022. Published by Oxford University Press. | ||
| 520 | |a OBJECTIVES: To assess the safety and pharmacokinetics (PK) of single-dose subcutaneous (SC) sarilumab or tocilizumab SC ± methotrexate (MTX) and to assess the pharmacodynamics (PD) of sarilumab SC or tocilizumab SC monotherapy in Japanese rheumatoid arthritis (RA) patients | ||
| 520 | |a METHODS: TDU13402 was a randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study (NCT01850680). Twenty-four patients (6 per treatment group) received sarilumab 50, 100, or 200 mg plus MTX or placebo (2 per cohort) on Day (D) 1; PK and safety were assessed through D57. PDY14191 was a randomized, open-label, single-dose study (NCT02404558). Thirty patients (15 per arm) received sarilumab 150 mg or tocilizumab 162 mg on D1; PK, PD, and safety were assessed through D43 | ||
| 520 | |a RESULTS: TDU13402: mean serum sarilumab exposure increased in a greater than dose proportional manner from 50 to 200 mg dose with no clinically meaningful increase in treatment-emergent adverse events (TEAEs). PDY14191: PK profiles of single-dose sarilumab 150 mg or tocilizumab 162 mg were similar; some numerical differences in PD profiles and TEAEs were observed. Neutrophil count decrease/neutropenia was the most frequently reported TEAE with sarilumab treatment in both studies | ||
| 520 | |a CONCLUSIONS: PK, PD, and safety profiles of single-dose sarilumab SC with/without MTX were consistent with results anticipated in Japanese patients with RA | ||
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