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Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.

Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.

期刊: Clinical pharmacology in drug development 日期: 2026-06-01 PMID: 42213484 DOI: 10.1002/cpdd.70070 浏览: 54
作者: Buckley SA, Al-Fayoumi S, Dean JP, Zhang J, Suthar P, Richard M
SA, B., S, A.F., JP, D., J, Z., P, S., & M, R. (2026). Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.. Clinical pharmacology in drug development. https://doi.org/10.1002/cpdd.70070
SA B, S AF, JP D, J Z, P S, M R. Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.. Clinical pharmacology in drug development. 2026; doi: 10.1002/cpdd.70070
SA B, S AF, JP D, et al. Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.[J]. Clinical pharmacology in drug development. 2026. DOI: 10.1002/cpdd.70070.
@article{sa2026,
  author = {Buckley SA and Al-Fayoumi S and Dean JP and Zhang J and Suthar P and Richard M},
  title = {Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.},
  journal = {Clinical pharmacology in drug development},
  year = {2026},
  doi = {10.1002/cpdd.70070},
  note = {PMID: 42213484},
}
TY  - JOUR
AU  - Buckley SA
AU  - Al-Fayoumi S
AU  - Dean JP
AU  - Zhang J
AU  - Suthar P
AU  - Richard M
TI  - Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data.
T2  - Clinical pharmacology in drug development
PY  - 2026
DO  - 10.1002/cpdd.70070
AN  - PMID:42213484
ER  - 

摘要

Pacritinib, an inhibitor of JAK2/IRAK1/ACVR1 that is devoid of JAK1 activity, approved for treating myelofibrosis in patients with severe thrombocytopenia, carries a label warning for QT interval prolongation. To evaluate the cardiac safety of pacritinib, a randomized, placebo- and active-controlled, single-dose thorough QT (TQT) study was conducted in healthy subjects, and a dose-finding study (PAC203) was conducted in patients with myelofibrosis. In the TQT study, 42 subjects received single doses of pacritinib 400 mg, moxifloxacin 400 mg (positive control), and placebo in a crossover design. The maximal placebo-corrected change in QT interval with pacritinib was -9.7 ms (90% confidence interval: -13.4, -6.1), and all upper confidence bounds were <10 ms. A small, clinically irrelevant inverse concentration-QTc relationship was observed. No subject administered pacritinib had a QTc interval using Fridericia's formula (QTcF) >480 ms or a change from baseline in QTcF >30 ms. Moreover, in the PAC203 trial, there was no correlation between pacritinib exposure and QTcF at weeks 12 or 24. Median QTcF changes from pre-dose to 4 h post-dose were minimal (+2.7 and -0.3 ms, respectively), and no dose-response relationship was identified. These findings suggest that pacritinib exposure is unlikely to be correlated with QT prolongation.

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