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An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants
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| Zeitschriftentitel: | The Journal of Clinical Pharmacology |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | The Journal of Clinical Pharmacology, 60, 2020, 11, S. 1519-1526 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Li, Jia Rockich, Kevin Yuska, Brad Zhou, Gongfu Epstein, Noam Punwani, Naresh Chen, Xuejun Yeleswaram, Swamy Li, Jia Rockich, Kevin Yuska, Brad Zhou, Gongfu Epstein, Noam Punwani, Naresh Chen, Xuejun Yeleswaram, Swamy |
|---|---|
| author |
Li, Jia Rockich, Kevin Yuska, Brad Zhou, Gongfu Epstein, Noam Punwani, Naresh Chen, Xuejun Yeleswaram, Swamy |
| spellingShingle |
Li, Jia Rockich, Kevin Yuska, Brad Zhou, Gongfu Epstein, Noam Punwani, Naresh Chen, Xuejun Yeleswaram, Swamy The Journal of Clinical Pharmacology An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants Pharmacology (medical) Pharmacology |
| author_sort |
li, jia |
| spelling |
Li, Jia Rockich, Kevin Yuska, Brad Zhou, Gongfu Epstein, Noam Punwani, Naresh Chen, Xuejun Yeleswaram, Swamy 0091-2700 1552-4604 Wiley Pharmacology (medical) Pharmacology http://dx.doi.org/10.1002/jcph.1653 <jats:title>Abstract</jats:title><jats:p>Parsaclisib, a selective, potent phosphatidylinositol 3‐kinase delta inhibitor being developed for the treatment of cancer and autoimmune diseases, is primarily metabolized by cytochrome P450 (CYP) 3A4. This study assessed the pharmacokinetics (PK) and safety of parsaclisib alone or combined with itraconazole (potent CYP3A inhibitor) or rifampin (potent CYP3A4 inducer) in healthy participants. In this open‐label, fixed‐sequence study, cohort 1 received oral parsaclisib 10 mg once daily on days 1 and 8 and oral itraconazole 200 mg once daily on days 4‐11; cohort 2 received oral parsaclisib 20 mg once daily on days 1 and 11 and oral rifampin 600 mg once daily on days 4‐12. Parsaclisib plasma concentration was tested and PK parameters calculated by noncompartmental analysis. Geometric mean ratios (GMRs) and 2‐sided 90% confidence intervals (CIs) were estimated by 2‐factor analysis of variance. Thirty‐six healthy participants were enrolled (18 per cohort). Parsaclisib maximum plasma drug concentration (C<jats:sub>max</jats:sub>) and area under the concentration‐time curve extrapolated to infinity (AUC<jats:sub>0‐∞</jats:sub>) were increased by 21% and 107% with concomitant itraconazole versus parsaclisib alone (GMR, 1.21; 90%CI, 1.14‐1.29; and 2.07; 90%CI, 1.97‐2.17, respectively). Parsaclisib C<jats:sub>max</jats:sub> and AUC were reduced by 43% and 77%, respectively, with concomitant rifampin versus parsaclisib alone (GMR, 0.57; 90%CI, 0.53‐0.60; and 0.23; 90%CI, 0.21‐0.24, respectively). Headache was the most common adverse event, reported by 13.9% of participants (all in cohort 2). Single‐dose parsaclisib alone or combined with itraconazole or rifampin appeared safe and well tolerated in healthy participants. Parsaclisib dose adjustment may be necessary with concomitant administration of strong CYP3A4 inhibitors or inducers.</jats:p> An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants The Journal of Clinical Pharmacology |
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| title |
An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_unstemmed |
An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_full |
An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_fullStr |
An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_full_unstemmed |
An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_short |
An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_sort |
an open‐label study to assess the effect of itraconazole and rifampin on parsaclisib pharmacokinetics when administered orally in healthy participants |
| topic |
Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1002/jcph.1653 |
| publishDate |
2020 |
| physical |
1519-1526 |
| description |
<jats:title>Abstract</jats:title><jats:p>Parsaclisib, a selective, potent phosphatidylinositol 3‐kinase delta inhibitor being developed for the treatment of cancer and autoimmune diseases, is primarily metabolized by cytochrome P450 (CYP) 3A4. This study assessed the pharmacokinetics (PK) and safety of parsaclisib alone or combined with itraconazole (potent CYP3A inhibitor) or rifampin (potent CYP3A4 inducer) in healthy participants. In this open‐label, fixed‐sequence study, cohort 1 received oral parsaclisib 10 mg once daily on days 1 and 8 and oral itraconazole 200 mg once daily on days 4‐11; cohort 2 received oral parsaclisib 20 mg once daily on days 1 and 11 and oral rifampin 600 mg once daily on days 4‐12. Parsaclisib plasma concentration was tested and PK parameters calculated by noncompartmental analysis. Geometric mean ratios (GMRs) and 2‐sided 90% confidence intervals (CIs) were estimated by 2‐factor analysis of variance. Thirty‐six healthy participants were enrolled (18 per cohort). Parsaclisib maximum plasma drug concentration (C<jats:sub>max</jats:sub>) and area under the concentration‐time curve extrapolated to infinity (AUC<jats:sub>0‐∞</jats:sub>) were increased by 21% and 107% with concomitant itraconazole versus parsaclisib alone (GMR, 1.21; 90%CI, 1.14‐1.29; and 2.07; 90%CI, 1.97‐2.17, respectively). Parsaclisib C<jats:sub>max</jats:sub> and AUC were reduced by 43% and 77%, respectively, with concomitant rifampin versus parsaclisib alone (GMR, 0.57; 90%CI, 0.53‐0.60; and 0.23; 90%CI, 0.21‐0.24, respectively). Headache was the most common adverse event, reported by 13.9% of participants (all in cohort 2). Single‐dose parsaclisib alone or combined with itraconazole or rifampin appeared safe and well tolerated in healthy participants. Parsaclisib dose adjustment may be necessary with concomitant administration of strong CYP3A4 inhibitors or inducers.</jats:p> |
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| author | Li, Jia, Rockich, Kevin, Yuska, Brad, Zhou, Gongfu, Epstein, Noam, Punwani, Naresh, Chen, Xuejun, Yeleswaram, Swamy |
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| description | <jats:title>Abstract</jats:title><jats:p>Parsaclisib, a selective, potent phosphatidylinositol 3‐kinase delta inhibitor being developed for the treatment of cancer and autoimmune diseases, is primarily metabolized by cytochrome P450 (CYP) 3A4. This study assessed the pharmacokinetics (PK) and safety of parsaclisib alone or combined with itraconazole (potent CYP3A inhibitor) or rifampin (potent CYP3A4 inducer) in healthy participants. In this open‐label, fixed‐sequence study, cohort 1 received oral parsaclisib 10 mg once daily on days 1 and 8 and oral itraconazole 200 mg once daily on days 4‐11; cohort 2 received oral parsaclisib 20 mg once daily on days 1 and 11 and oral rifampin 600 mg once daily on days 4‐12. Parsaclisib plasma concentration was tested and PK parameters calculated by noncompartmental analysis. Geometric mean ratios (GMRs) and 2‐sided 90% confidence intervals (CIs) were estimated by 2‐factor analysis of variance. Thirty‐six healthy participants were enrolled (18 per cohort). Parsaclisib maximum plasma drug concentration (C<jats:sub>max</jats:sub>) and area under the concentration‐time curve extrapolated to infinity (AUC<jats:sub>0‐∞</jats:sub>) were increased by 21% and 107% with concomitant itraconazole versus parsaclisib alone (GMR, 1.21; 90%CI, 1.14‐1.29; and 2.07; 90%CI, 1.97‐2.17, respectively). Parsaclisib C<jats:sub>max</jats:sub> and AUC were reduced by 43% and 77%, respectively, with concomitant rifampin versus parsaclisib alone (GMR, 0.57; 90%CI, 0.53‐0.60; and 0.23; 90%CI, 0.21‐0.24, respectively). Headache was the most common adverse event, reported by 13.9% of participants (all in cohort 2). Single‐dose parsaclisib alone or combined with itraconazole or rifampin appeared safe and well tolerated in healthy participants. Parsaclisib dose adjustment may be necessary with concomitant administration of strong CYP3A4 inhibitors or inducers.</jats:p> |
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| spelling | Li, Jia Rockich, Kevin Yuska, Brad Zhou, Gongfu Epstein, Noam Punwani, Naresh Chen, Xuejun Yeleswaram, Swamy 0091-2700 1552-4604 Wiley Pharmacology (medical) Pharmacology http://dx.doi.org/10.1002/jcph.1653 <jats:title>Abstract</jats:title><jats:p>Parsaclisib, a selective, potent phosphatidylinositol 3‐kinase delta inhibitor being developed for the treatment of cancer and autoimmune diseases, is primarily metabolized by cytochrome P450 (CYP) 3A4. This study assessed the pharmacokinetics (PK) and safety of parsaclisib alone or combined with itraconazole (potent CYP3A inhibitor) or rifampin (potent CYP3A4 inducer) in healthy participants. In this open‐label, fixed‐sequence study, cohort 1 received oral parsaclisib 10 mg once daily on days 1 and 8 and oral itraconazole 200 mg once daily on days 4‐11; cohort 2 received oral parsaclisib 20 mg once daily on days 1 and 11 and oral rifampin 600 mg once daily on days 4‐12. Parsaclisib plasma concentration was tested and PK parameters calculated by noncompartmental analysis. Geometric mean ratios (GMRs) and 2‐sided 90% confidence intervals (CIs) were estimated by 2‐factor analysis of variance. Thirty‐six healthy participants were enrolled (18 per cohort). Parsaclisib maximum plasma drug concentration (C<jats:sub>max</jats:sub>) and area under the concentration‐time curve extrapolated to infinity (AUC<jats:sub>0‐∞</jats:sub>) were increased by 21% and 107% with concomitant itraconazole versus parsaclisib alone (GMR, 1.21; 90%CI, 1.14‐1.29; and 2.07; 90%CI, 1.97‐2.17, respectively). Parsaclisib C<jats:sub>max</jats:sub> and AUC were reduced by 43% and 77%, respectively, with concomitant rifampin versus parsaclisib alone (GMR, 0.57; 90%CI, 0.53‐0.60; and 0.23; 90%CI, 0.21‐0.24, respectively). Headache was the most common adverse event, reported by 13.9% of participants (all in cohort 2). Single‐dose parsaclisib alone or combined with itraconazole or rifampin appeared safe and well tolerated in healthy participants. Parsaclisib dose adjustment may be necessary with concomitant administration of strong CYP3A4 inhibitors or inducers.</jats:p> An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants The Journal of Clinical Pharmacology |
| spellingShingle | Li, Jia, Rockich, Kevin, Yuska, Brad, Zhou, Gongfu, Epstein, Noam, Punwani, Naresh, Chen, Xuejun, Yeleswaram, Swamy, The Journal of Clinical Pharmacology, An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants, Pharmacology (medical), Pharmacology |
| title | An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_full | An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_fullStr | An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_full_unstemmed | An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_short | An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| title_sort | an open‐label study to assess the effect of itraconazole and rifampin on parsaclisib pharmacokinetics when administered orally in healthy participants |
| title_unstemmed | An Open‐Label Study to Assess the Effect of Itraconazole and Rifampin on Parsaclisib Pharmacokinetics When Administered Orally in Healthy Participants |
| topic | Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1002/jcph.1653 |