Effect of Multiple Doses of Modafinil on the Pharmacokinetics of Single Dose Lorlatinib in Healthy Participants
Summary
The primary purpose of the study is to characterize the safety profile of lorlatinib in the presence of a moderate CYP3A4/5 inducer, modafinil. In another drug-drug interaction study for lorlatinib coadministered with a strong CYP3A4/5 inducer, rifampin, all participants experienced increases in liver enzymes after receiving the combination of a single dose lorlatinib (100 mg) with rifampin (600 mg daily (QD)) after multiple doses of rifampin. The AST and ALT continued to increase over the next 24-48 hours, but recovered below the upper limit of normal for all participants upon discontinuation of rifampin. We hypothesize the combination of lorlatinib with the moderate CYP3A inducer modafinil will not have a safety findings related to liver enzyme elevation similar to what occurred in the study with rifampin and lorlatinib.
Timeline
- Start
- 2019-08-22
- Primary completion
- 2019-12-09
- Completion
- 2019-12-09
Publications
- Rodrigues AD, Wood LS, Vourvahis M, Rowland A. Leveraging Human Plasma-Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Cytochrome P450 3A4 by Modafinil. Clin Pharmacol Ther. 2022 Feb;111(2):425-434. doi: 10.1002/cpt.2440. Epub 2021 Nov 2.
- Li J, Pithavala YK, Gong J, LaBadie RR, Mfopou JK, Chen J. The Effect of Modafinil on the Safety and Pharmacokinetics of Lorlatinib: A Phase I Study in Healthy Participants. Clin Pharmacokinet. 2021 Oct;60(10):1303-1312. doi: 10.1007/s40262-021-01026-w. Epub 2021 May 3.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lorlatinib | Small molecule | 50 mg | Oral |
| Subject | Lorlatinib | Small molecule | 75 mg | Oral |
| Subject | Lorlatinib | Small molecule | 100 mg | Oral |
Indications
No indication recorded.