Atogepant and Sumatriptan: No Clinically Relevant Drug–Drug Interactions in a Randomized, Open-Label, Crossover Trial

Figures & data

Figure 1. Participant flow.

PK: Pharmacokinetics.

Table 1. Demographics and baseline characteristics (safety population).

	Atogepant 60 mg (n = 28)	Sumatriptan 100 mg (n = 29)	Atogepant 60 mg + sumatriptan 100 mg (n = 27)
Age (years), mean (SD)	33.7 (6.1)	32.8 (6.8)	33.6 (6.2)
Male, n (%)	15 (53.6)	17 (58.6)	15 (55.6)
Race, n (%)
White	20 (71.4)	21 (72.4)	20 (74.1)
Black/African–American	8 (28.6)	8 (27.6)	7 (25.9)
Hispanic ethnicity, n (%)	23 (82.1)	24 (82.8)	22 (81.5)
BMI (kg/m^2), mean (SD)	24.9 (2.5)	24.7 (2.6)	25.0 (2.5)

BMI: Body mass index; SD: Standard deviation.

Figure 2. Mean (± standard deviation) plasma atogepant concentration–time profile following single-dose oral administration of 60 mg of atogepant alone (n = 28) or when coadministered with single-dose oral administration of 100 mg sumatriptan (n = 27) to fasted healthy participants (linear scale).

Table 2. Pharmacokinetic parameters of atogepant following single-dose oral administration of atogepant alone or when coadministered with sumatriptan.

PK parameter, mean (SD)	Atogepant 60 mg (n = 28)	Atogepant 60 mg + sumatriptan 100 mg (n = 27)
Cmax (ng/ml)	841 (436)	668 (363)
AUC0-t (ng·h/ml)	3870 (1970)	3700 (1910)
AUC0-∞ (ng·h/ml)	3900 (1990)	3730 (1930)
Tmax (h)^†	1.50 (0.50–4.00)	3.00 (1.00–4.00)
t1/2 (h)	8.24 (2.98)	8.67 (3.91)
Vz/F (l)	224 (120)	233 (120)
CL/F (l/h)	19.3 (9.30)	20.4 (10.8)

† Median (range).

AUC_0-t: Area under the plasma drug concentration–time curve from time 0 to time t; AUC_0-∞: Area under the plasma drug concentration–time curve from time 0 to infinity; CL/F: Apparent total body clearance of drug from plasma after extravascular administration; C_max: Maximum plasma drug concentration; PK: Pharmacokinetic; SD: Standard deviation; t_1/2: Apparent terminal elimination half-life; T_max: Time to maximum plasma drug concentration; V_Z/F: Apparent volume of distribution during the terminal phase after extravascular administration.

Figure 3. Mean (± standard deviation) plasma sumatriptan concentration–time profile following single-dose oral administration of 100 mg sumatriptan alone (n = 29) or when coadministered with single-dose oral administration of 60 mg atogepant (n = 27) to fasted healthy participants (linear scale).

Table 3. Pharmacokinetic parameters of sumatriptan following single-dose administration of sumatriptan alone or when coadministered with atogepant.

PK parameter, mean (SD)	Sumatriptan 100 mg (n = 29)	Atogepant 60 mg + sumatriptan 100 mg (n = 27)
Cmax (ng/ml)	74.1 (33.1)	71.3 (36.2)
AUC0-t (ng·h/ml)	306 (87.6)	311 (91.4)
AUC0-∞ (ng·h/ml)^†	307 (94.2)	317 (97.1)
Tmax (h)^‡	2.00 (0.50–4.00)	2.00 (0.50–4.00)
t1/2 (h)^†	3.89 (3.21)	4.14 (4.63)
Vz/F (l)^†	1800 (1080)	1990 (1810)
CL/F (l/h)^†	356 (110)	345 (106)

† n = 24; five participants in the sumatriptan 100 mg alone group and three in the atogepant + sumatriptan coadministration group were excluded from descriptive statistics calculations; t_1/2, AUC_0-∞, CL/F, Vz/F were not determined if adjusted R² was <0.8.

‡ Median (range).

AUC_0-t: Area under the plasma drug concentration–time curve from time 0 to time t; AUC_0-∞: Area under the plasma drug concentration–time curve from time 0 to infinity; CL/F: Apparent total body clearance of drug from plasma after extravascular administration; C_max: Maximum plasma drug concentration; PK: Pharmacokinetic; SD: Standard deviation; t_1/2: Apparent terminal elimination half-life; T_max: Time to maximum plasma drug concentration; V_Z/F: Apparent volume of distribution during the terminal phase after extravascular administration.

Table 4. Statistical analysis of pharmacokinetic parameters: comparison of atogepant administered alone and when coadministered with sumatriptan and comparison of sumatriptan administered alone and when coadministered with atogepant.

	Testgeometric LSM	Referencegeometric LSM	GMR (test/reference)	90% CIlower limit	90% CIupper limit
Atogepant PK parameter	Atogepant 60 mg + sumatriptan 100 mg	Atogepant 60 mg
Cmax (ng/ml)	616	786	0.78	0.69	0.89
AUC0-t (ng·h/ml)	3410	3590	0.95	0.86	1.05
AUC0-∞ (ng·h/ml)	3440	3620	0.95	0.86	1.05
Sumatriptan PK parameter	Sumatriptan 100 mg + atogepant 60 mg	Sumatriptan 100 mg
Cmax (ng/ml)	62.0	64.9	0.95	0.85	1.07
AUC0-t (g·h/ml)	292	287	1.02	0.96	1.08
AUC0-∞ (ng·h/ml)	303	296	1.02	0.97	1.08

AUC_0-t: Area under the plasma drug concentration–time curve from time 0 to time t; AUC_0-∞: Area under the plasma drug concentration–time curve from time 0 to infinity; C_max: Maximum plasma drug concentration; GMR: Geometric means ratio; LSM: Least squares mean; PK: Pharmacokinetic.

Data availability

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