ArticleClinical pharmacokinetics2021
The Effect of Modafinil on the Safety and Pharmacokinetics of Lorlatinib: A Phase I Study in Healthy Participants.
Article in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03961997 (PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD STUDY TO INVESTIGATE THE EFFECT OF MULTIPLE DOSES OF MODAFINIL ON THE PHARMACOKINETICS OF SINGLE DOSE LORLATINIB), which is not on this map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1, open-label, fixed sequence, 2-period study to investigate the effect of multiple doses of modafinil on the pharmacokinetics of single dose lorlatinib (pf-06463922) in healthy participants
Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Evaluation of the absolute oral bioavailability of the anaplastic lymphoma kinase/c-ROS oncogene 1 kinase inhibitor lorlatinib in healthy participants.Cancer chemotherapy and pharmacology · 2022Trial
- Tyrosine-kinase inhibitors for lung or breast cancer and drug-drug interactions: a clinical guide.Oncology reviews · 2025Review
- Interindividual variability in CYP3A-mediated venetoclax metabolism in vitro and in vivo in patients with chronic lymphocytic leukemia.Clinical and translational science · 2024Article
- Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer.Clinical drug investigation · 2024Review
- Evaluation of the Effect of Lorlatinib on CYP2B6, CYP2C9, UGT, and P-Glycoprotein Substrates in Patients with Advanced Non-Small Cell Lung Cancer.Clinical pharmacokinetics · 2024Article
- Recent Advances in the Management of Adverse Events Associated with Lorlatinib.OncoTargets and therapy · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveLorlatinib is a third-generation tyrosine kinase inhibitor approved for the second-line treatment of patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. Lorlatinib is metabolized by cytochrome P450 (CYP) 3A and contraindicated with strong CYP3A inducers because of significant transaminase elevation. This phase I, open-label, two-period study evaluated the impact of a moderate CYP3A inducer, modafinil, on the safety and pharmacokinetics of lorlatinib.
methodsHealthy participants received single-dose oral lorlatinib (50 mg [n = 2], 75 mg [n = 2], or 100 mg [n = 2 + 10 in an expanded cohort]) in Period 1 followed by modafinil 400 mg/day (days 1-19) and single-dose lorlatinib (day 15, same dose as previous) both orally in Period 2. Blood samples were collected for 120 h after each dose of lorlatinib.
resultsOf 16 participants, ten completed the study; six participants, all in the expanded 100-mg cohort, discontinued because of adverse events during the modafinil lead-in dosing period. Single doses of lorlatinib 50-100 mg were well tolerated when administered alone and in the presence of steady-state modafinil. Of the ten participants who completed the study, all had transaminase values within normal limits during the combination of lorlatinib with modafinil. The ratios of the adjusted geometric means (90% confidence interval) for lorlatinib area under the plasma concentration-time profile extrapolated to infinity and maximum plasma concentration were 76.69% (70.15-83.83%) and 77.78% (65.92-91.77), respectively, when lorlatinib 100 mg was co-administered with steady-state modafinil compared with lorlatinib administration alone.
conclusionLorlatinib 100 mg may be safely co-administered with moderate CYP3A inducers. CLINICAL
trial registrationClinicalTrials.gov NCT03961997; registered 23 May, 2019.
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