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Abstract Details

Evaluation of Pharmacokinetic Interactions and Safety of Atogepant Coadministered With Quinidine Gluconate
Headache
Headache Posters (7:00 AM-5:00 PM)
102
To evaluate effects of P-glycoprotein (P-gp) inhibition by quinidine gluconate on pharmacokinetics (PK) and safety of atogepant.
Atogepant, an oral calcitonin gene–related receptor antagonist in development for preventive treatment of migraine, is a P-gp substrate.

In this phase 1, single-center, single-sequence, open-label, 2-intervention, drug-drug interaction study, healthy adults received atogepant 60mg on day 1, quinidine gluconate 324mg twice-daily on day 8, and 648mg twice-daily on days 9–12, with atogepant 60mg coadministered on day 11. Plasma samples were collected on days 1 and 11. Atogepant PK parameters calculated were peak plasma concentration (Cmax); time to Cmax (tmax); and area under plasma concentration-time curve from time 0 to time t (AUC0-t) and infinity (AUC0-∞). PK parameters of atogepant coadministered with quinidine gluconate vs atogepant administered alone were compared using mixed-effects model. Statistical significance was achieved if 90% confidence intervals (CIs) for least squares geometric mean ratios (GMRs) of PK parameter values for atogepant coadministered with quinidine gluconate to atogepant administered alone were within 80%–125%. Safety assessments included clinical laboratory values, vital signs, electrocardiograms, and treatment-emergent adverse events (TEAEs).

Of 33 enrolled participants (mean age 30.3 years; 72.7% males), 23 (69.7%) completed the study; 10 discontinued because of TEAEs (all electrocardiogram QT prolongation during quinidine gluconate administration). Atogepant median tmax was 1.50 hours with or without quinidine gluconate coadministration. GMRs (90% CI) were 104.41 (89.17–122.25) for Cmax, 125.49 (110.21–142.88) for AUC0-t, and 125.91 (110.56–143.40) for AUC0-∞; changes in AUC were statistically significant. TEAEs were mostly related to quinidine gluconate administration.
Atogepant Cmax increased 4.4% and AUC increased approximately 25% when coadministered with quinidine gluconate; however, these changes are not expected to be clinically significant.
Authors/Disclosures

PRESENTER
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