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Clinical Trial
. 2020 Sep;40(9):827-838.
doi: 10.1007/s40261-020-00937-z.

Investigation of Potential Drug-Drug Interactions between Peficitinib (ASP015K) and Methotrexate in Patients with Rheumatoid Arthritis

Tong Zhu  1 , Selina Moy  2 , Udaya Valluri  3 , Ying Cao  3 , Wenhui Zhang  3 , Taiji Sawamoto  4 , Vishala Chindalore  5 , Bola Akinlade  3   6
Affiliations
Clinical Trial

Investigation of Potential Drug-Drug Interactions between Peficitinib (ASP015K) and Methotrexate in Patients with Rheumatoid Arthritis

Tong Zhu et al. Clin Drug Investig. 2020 Sep.

Abstract

Background: Methotrexate is frequently used to treat rheumatoid arthritis. Peficitinib (ASP015K; Smyraf®), an oral Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis, may be coadministered with methotrexate.

Objective: The objective of this study was to investigate potential drug-drug interactions of peficitinib with methotrexate and the short-term safety of coadministration.

Patients and methods: This phase I, open-label, single-sequence study included patients with rheumatoid arthritis taking a stable dose of methotrexate. Patients received their prescribed methotrexate dose (Day 1) and then peficitinib (100 mg) twice daily from Day 3 until the morning of Day 9; a second methotrexate dose was coadministered with peficitinib on Day 8. Serial blood samples were collected for methotrexate concentration after dosing on Days 1 (methotrexate alone) and 8 (methotrexate plus peficitinib) and for peficitinib concentration after dosing on Days 7 (peficitinib alone) and 8 (methotrexate plus peficitinib). Pre-dose concentrations of peficitinib were measured (Days 3-8).

Results: Peficitinib concentrations reached steady state on Day 5. Administration of peficitinib did not result in changes to methotrexate area under the concentration-time curve from time zero to infinity or maximum observed concentration following a methotrexate dose (15-25 mg), and there was no significant effect of methotrexate (15-25 mg) on peficitinib area under the concentration-time curve within a 12-hour dosing interval. There were no new tolerability or safety signals after coadministration of peficitinib and methotrexate. One patient experienced two serious adverse events and withdrew from the study without receiving peficitinib.

Conclusions: Pharmacokinetic results showed no significant interactions between peficitinib and methotrexate. CLINICALTRIALS.

Gov identifier: NCT01754805.

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Conflict of interest statement

Tong Zhu, Udaya Valluri and Ying Cao are employees of Astellas Pharma Global Development Inc. Wenhui Zhang was an employee of Astellas Pharma Global Development Inc. at the time of the study. Selina Moy is an employee of Astellas Research Institute of America. Taiji Sawamoto is an employee of Astellas Pharma Inc. Bola Akinlade was an employee of Astellas Pharma Global Development Inc. at the time of the study, and is now an employee of Regeneron Pharmaceuticals; he reports no conflicts of interest that are directly relevant to the content of this study. Vishala Chindalore is an employee of Pinnacle Research Group/Anniston Medical Clinic, which received funding from Astellas to conduct the study.

Figures

Fig. 1
Fig. 1
Treatment periods used for drug–drug interaction study and analyses. BID twice daily. Patients received their usual prescribed methotrexate dose (15–25 mg) on Day 1 and a second prescribed dose on Day 8
Fig. 2
Fig. 2
Patient flow through the study. AE adverse event, PKAS pharmacokinetic analysis set, SAF safety analysis set
Fig. 3
Fig. 3
a Mean (± standard deviation) dose-normalized plasma methotrexate concentration–time profile on Days 1 (alone) and 8 (in combination with peficitinib). b Mean (± standard deviation) plasma peficitinib concentration vs time profile on Days 7 (peficitinib alone) and 8 (in combination with methotrexate). Concentrations below the lower limit of quantification (methotrexate = 1 ng/mL; peficitinib = 0.25 ng/mL) were set to 0
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References

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