Evidence map›Paper›PMID 39288032›Full record

Trial reportClinical and translational science2024

Drug-drug interactions of icenticaftor (QBW251) with a 5-probe cytochrome P450 cocktail and oral contraceptives.

Felix Huth, Ulrike Glaenzel, Anton Drollmann, Wendy Weis, Julia Zack, Lidiya Bebrevska

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Felix HuthNovartis Pharma AG, Basel, Switzerland.ORCID 0000-0002-7121-4394
Ulrike GlaenzelNovartis Pharma AG, Basel, Switzerland.
Anton DrollmannNovartis Pharma AG, Basel, Switzerland.
Wendy WeisNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Julia ZackNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Lidiya BebrevskaNovartis Pharma AG, Basel, Switzerland.

Funding

Novartis Pharma AG
6 · The paper itself

Abstract

A drug-drug interaction (DDI) study was conducted to evaluate the effect of icenticaftor (QBW251) on the pharmacokinetics (PK) of a 5-probe cytochrome P450 (CYP) substrate cocktail, guided by in vitro studies in human hepatocytes and liver microsomes. Another DDI study investigated the effect of icenticaftor on the PK and pharmacodynamics (PD) of a monophasic oral contraceptive (OC) containing ethinyl estradiol (EE) and levonorgestrel (LVG) in premenopausal healthy female subjects. The static-mechanistic DDI assessment indicated that icenticaftor may moderately induce the metabolic clearance of co-medications metabolized by CYP3A4 (area under the concentration-time curve [AUC] ratio: 0.47) and potentially CYP2C; icenticaftor may also weakly inhibit the metabolic clearance of co-medications metabolized by CYP1A2 and CYP3A4 (AUC ratio: 1.35 and 1.86, respectively) and moderately inhibit CYP2B6 (AUC ratio: 2.11). In the CYP substrate cocktail DDI study, icenticaftor 300 mg twice daily (b.i.d.) moderately inhibited CYP1A2 (AUC ratio: 3.35) and CYP2C19 (AUC ratio: 2.70). As expected from the results of the in vitro studies, weak induction was observed for CYP3A4 (AUC ratio: 0.51) and CYP2C8 (AUC ratio: 0.66). In the OC DDI study, co-administration of icenticaftor 450 mg b.i.d. with monophasic OC containing 30-μg EE and 150-μg LVG once daily reduced the plasma exposure of both components by approximately 50% and led to increased levels of follicle-stimulating hormone and luteinizing hormone. These results provide valuable guidance for the use of icenticaftor in patients taking concomitant medications that are substrates of CYP enzymes or patients using OCs.

Indexed as

Contraceptives, Oral, CombinedDrug InteractionsEthinyl EstradiolAdolescentAdultArea Under CurveContraceptives, OralCytochrome P-450 Enzyme SystemDrug CombinationsFemaleHealthy VolunteersHepatocytesHumansLevonorgestrelMicrosomes, LiverYoung AdultContraceptives, OralContraceptives, Oral, CombinedCytochrome P-450 Enzyme SystemDrug CombinationsEthinyl Estradiolethinyl estradiol, levonorgestrel drug combinationLevonorgestrel

Identifiers

PMID39288032
PMCPMC11407298

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Registered trials

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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.