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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
Atogepant, an oral calcitonin gene–related receptor antagonist in development for preventive treatment of migraine, is a P-gp substrate.
To evaluate effects of P-glycoprotein (P-gp) inhibition by quinidine gluconate on pharmacokinetics (PK) and safety of atogepant.

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
Ramesh *use 388303 Boinpally
PRESENTER
Ramesh Boinpally has received personal compensation for serving as an employee of Allergan/Abbvie. Ramesh Boinpally has stock in Abbvie. Ramesh Boinpally has stock in Allergan. Ramesh Boinpally has received intellectual property interests from a discovery or technology relating to health care.
Clint Forsythe (AbbVie) Clint Forsythe has received personal compensation for serving as an employee of Allergan. Clint Forsythe has received personal compensation for serving as an employee of AbbVie.
Lisa Borbridge (AbbVie) Lisa Borbridge has received personal compensation for serving as an employee of AbbVie. Lisa Borbridge has received stock or an ownership interest from AbbVie.
Veronica Wangsadipura (AbbVie) Veronica Wangsadipura has received personal compensation for serving as an employee of AbbVie. Veronica Wangsadipura has received stock or an ownership interest from AbbVie.
Matthew Butler Matthew Butler has received personal compensation for serving as an employee of Allergan / Abbvie. Matthew Butler has received stock or an ownership interest from Allergan/Abbvie.