Trial reportEuropean journal of clinical pharmacology2019
Siponimod pharmacokinetics, safety, and tolerability in combination with the potent CYP3A4 inhibitor itraconazole in healthy subjects with different CYP2C9 genotypes.
Trial report in European journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- PBPK Modeling and Clinical Data Reveal Reduced Impact of CYP3A4 and CYP2C9 Inhibitors on Elimination of Siponimod.Clinical and translational science · 2026Article
- The Impact of CYP2C9*11 Allelic Variant on the Pharmacokinetics of Phenytoin and (S)-Warfarin.Clinical pharmacology and therapeutics · 2022Article
- Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents.Clinical and translational science · 2022Article
- Pharmacokinetic Characteristics of Siponimod in Healthy Volunteers and Patients With Multiple Sclerosis: Analyses of Published Clinical Trials.Frontiers in pharmacology · 2022Article
- Siponimod: A Review in Secondary Progressive Multiple Sclerosis.CNS drugs · 2020Review
- Prediction of the Impact of Cytochrome P450 2C9 Genotypes on the Drug-Drug Interaction Potential of Siponimod With Physiologically-Based Pharmacokinetic Modeling: A Comprehensive Approach for Drug Label Recommendations.Clinical pharmacology and therapeutics · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate the PK and safety of siponimod, a substrate of CYP2C9/3A4, in the presence or absence of a CYP3A4 inhibitor, itraconazole.
methodsThis was an open-label study in healthy subjects (aged 18-50 years; genotype: CYP2C9 *1*2 [cohort 1; n = 17] or *1*3 [cohort 2; n = 13]). Subjects received siponimod 0.25-mg single dose in treatment period 1 (days 1-14), itraconazole 100 mg twice daily in treatment period 2 (days 15-18), and siponimod 0.25-mg single dose (day 19) with itraconazole until day 31 (cohort 1) or day 35 (cohort 2) in treatment period 3. PK of siponimod alone and with itraconazole and safety were assessed.
resultsOverall, 29/30 subjects completed the study. In treatment period 1, geometric mean AUC
conclusionsThe minor albeit significant reduction in plasma exposure of siponimod and its metabolites by itraconazole was unexpected. While the reason is unclear, the results suggest that coadministration of the two drugs would not cause a considerable increase of siponimod exposure independent of CYP2C9 genotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.