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Abstract Details

Mass Balance and Metabolism of Carbon-14 Atogepant in Healthy Male Participants
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064
Atogepant is an oral calcitonin gene–related peptide receptor antagonist in development for preventive treatment of migraine.
Single-center, open-label, phase 1 study to examine elimination, metabolism, and mass balance of 14C-atogepant. 
Healthy males (N=6) aged 19–55 years received oral, single-dose 50mg (≈200µCi) 14C-atogepant following ≈10-hour overnight fast. Blood, urine, feces, and emesis were collected up to 28 days for pharmacokinetic analysis. Concentrations of atogepant, metabolites, and radioactivity were determined; metabolites were characterized where possible.

Of 6 participants enrolled (mean age 33.3 years; body mass index 28.83kg/m2), 5 completed the study. One participant withdrew (day 7; family emergency) after receiving atogepant. Median times to maximum plasma concentration were 1.0 and 1.5 hours postdose, mean terminal elimination half-life was 18.46 and 11.64 hours for atogepant and total radioactivity, respectively. Mean atogepant/total radioactivity ratio for systemic exposure (area under concentration-time curve) was ≈0.75, indicating unchanged parent drug was the major circulating species in plasma. Approximately 81% of radioactivity was recovered in feces, 8% in urine. Mean total radioactivity recovery in feces and urine was ≈89% over 336 hours after dosing. In feces, 42% of the dose was recovered as parent drug due to unabsorbed drug, biliary excretion, intestinal secretion, or combination. Atogepant and metabolite M23 were the only radiometric peaks in plasma; at least 11 metabolites were detected in feces (each <10% of radioactive dose). Metabolite M23 represented ≈15% of radioactive exposure in plasma, was not long-lasting, and tentatively characterized as dioxygenated methylated glucuronide of atogepant. No treatment-emergent adverse events or serious adverse events occurred. No clinically meaningful changes in laboratory, vital, or electrocardiogram parameters were observed.

Following a single, oral, 50mg dose of 14C-atogepant, atogepant was the major circulating species in plasma. Radioactive atogepant was moderately well absorbed and primarily excreted in feces as unchanged drug (42%) and several minor metabolites.
Authors/Disclosures
Josh Rowe (Abbvie)
PRESENTER
Josh Rowe has received personal compensation for serving as an employee of Abbvie. Josh Rowe has received stock or an ownership interest from Abbvie.
Hon Chan (AbbVie) Hon Chan has received personal compensation for serving as an employee of Allergan / AbbVie. Hon Chan has received stock or an ownership interest from Allergan\AbbVie.
PUSHPA CHANDRASEKAR (Abbvie) PUSHPA CHANDRASEKAR has received personal compensation for serving as an employee of AbbVie. PUSHPA CHANDRASEKAR has received stock or an ownership interest from AbbVie.
Jonathan Rojo (Abbvie) Jonathan Rojo has received personal compensation for serving as an employee of Allergan/Abbvie, Inc..
Ramesh *use 388303 Boinpally 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.