Ticagrelor shows no clinically meaningful interaction with fazamorexant
A phase I study found weak CYP3A4 inhibition by ticagrelor left fazamorexant's overall drug exposure unchanged, with only a 14% rise in peak concentration.
Executive Summary
- A phase I, open-label study examined whether ticagrelor, a blood thinner that weakly inhibits a liver enzyme, changes how the body processes fazamorexant, an investigational dual orexin receptor antagonist for insomnia.
- Co-administration nudged fazamorexant's peak concentration upward but left its total drug exposure essentially unchanged, and the combination was tolerated without new safety concerns.
- The result supports using fazamorexant alongside weak CYP3A4 inhibitors such as ticagrelor without a dose adjustment, a practical labeling question for a drug whose late-stage insomnia trials have already completed.
The question
Fazamorexant, a dual orexin receptor antagonist (a drug that blocks both orexin receptor subtypes to promote sleep), is metabolized in the body through the CYP3A4 enzyme pathway. Because many common medications, including the antiplatelet drug ticagrelor, weakly inhibit CYP3A4, developers need to establish whether combining the two changes fazamorexant's blood levels enough to require a different dose. This trial, registered as NCT06671470 and sponsored by Shanghai Haiyan Pharmaceutical Technology, was designed to answer that specific interaction question rather than to test fazamorexant's effect on sleep. Drug-drug+1Drug-drug interaction between ticagrelor and fazamorexant: pharmacokinetic alterations in healthy subjects from a phase I, open-label, fixed-sequence study.Jul 21, 2026A Drug-drug Interaction Study of YZJ-1139 Tablets and Ticagrelor Tablets in Healthy SubjectsNCT06671470
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
How it was done
The study used a single-center, open-label, non-randomized, fixed-sequence design in 24 healthy volunteers. Subjects received a single 20 mg oral dose of fazamorexant alone on day one, then a six-day regimen of ticagrelor (90 mg twice daily) to reach steady state, with a second fazamorexant dose co-administered on day six. Investigators measured fazamorexant's area under the concentration-time curve to the last measurable point (AUC0-t) and to infinity (AUC0-inf), maximum concentration (Cmax), and time to maximum concentration (Tmax), and recorded adverse events as a secondary measure. The trial enrolled 27 subjects on the registry and completed with a primary completion date of September 13, 2024. Drug-drug+1Drug-drug interaction between ticagrelor and fazamorexant: pharmacokinetic alterations in healthy subjects from a phase I, open-label, fixed-sequence study.Jul 21, 2026A Drug-drug Interaction Study of YZJ-1139 Tablets and Ticagrelor Tablets in Healthy SubjectsNCT06671470
The result
Ticagrelor co-administration increased fazamorexant's Cmax by approximately 14% (90% confidence interval: 100.92 to 129.07). AUC0-t (90% CI: 86.44 to 125.58) and AUC0-inf (90% CI: 85.60 to 124.53) remained essentially unchanged, and Tmax showed no statistical difference (P = 0.665). Fazamorexant was generally safe and well tolerated both alone and combined with ticagrelor. The peak-concentration shift moved without a corresponding change in total exposure, the measure that typically drives dosing decisions. Drug-drugDrug-drug interaction between ticagrelor and fazamorexant: pharmacokinetic alterations in healthy subjects from a phase I, open-label, fixed-sequence study.Jul 21, 2026
What it means for use
The study authors concluded that co-administering weak CYP3A4 inhibitors with fazamorexant is not expected to produce clinically significant drug interactions, and no dosage adjustment is required when the two are used together. That conclusion matters because fazamorexant's late-stage insomnia program establishes the drug's core efficacy and safety case separately from this interaction question. This trial instead fills in a labeling and real-world-use gap: whether a common co-medication changes how the drug should be dosed. Drug-drug+1Drug-drug interaction between ticagrelor and fazamorexant: pharmacokinetic alterations in healthy subjects from a phase I, open-label, fixed-sequence study.Jul 21, 2026A Drug-drug Interaction Study of YZJ-1139 Tablets and Ticagrelor Tablets in Healthy SubjectsNCT06671470
Where it sits
Fazamorexant belongs to a small class of dual orexin receptor antagonists, a group of drugs that block both orexin receptor subtypes to promote sleep. This drug-interaction study is part of the sponsor's broader pharmacokinetic characterization of fazamorexant, which has included renal-impairment, hepatic-impairment, and other drug-interaction studies alongside its insomnia efficacy program, and does not itself compete with other orexin-pathway programs in development. Drug-drug+1Drug-drug interaction between ticagrelor and fazamorexant: pharmacokinetic alterations in healthy subjects from a phase I, open-label, fixed-sequence study.Jul 21, 2026A Drug-drug Interaction Study of YZJ-1139 Tablets and Ticagrelor Tablets in Healthy SubjectsNCT06671470
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.