US-12622897-B2 - Methods of treating migraine

Abstract

The present disclosure provides methods for the treatment of migraine by the administration of atogepant or a pharmaceutically acceptable salt thereof.

Inventors

• Ramesh BOINPALLY
• Joel Trugman

Assignees

• ALLERGAN PHARMACEUTICALS INTERNATIONAL LIMITED

Dates

Publication Date

20260512

Application Date

20250218

Claims (10)

1. 1 . A method for the preventive treatment of migraine in a patient undergoing concurrent treatment with an OATP inhibitor, the method comprising orally administering a therapeutically effective dose of 10 mg atogepant once daily to the patient, wherein the patient's migraines are safely and effectively treated.
2. 2 . The method according to claim 1 , wherein co-administration of atogepant with the OATP inhibitor results in an increase in atogepant C max in the patient of about 2.2-fold relative to administration of atogepant alone.
3. 3 . The method according to claim 1 , wherein co-administration of atogepant with the OATP inhibitor results in an increase in atogepant AUC in the patient of about 2.8-fold relative to administration of atogepant alone.
4. 4 . The method according to claim 1 , wherein the OATP inhibitor is rifampin.
5. 5 . The method according to claim 1 , wherein the migraine is episodic migraine.
6. 6 . A method for the preventive treatment of migraine in a patient undergoing concurrent treatment with an OATP inhibitor, the method comprising orally administering a therapeutically effective dose of 30 mg atogepant once daily to the patient, wherein the patient's migraines are safely and effectively treated.
7. 7 . The method according to claim 6 , wherein co-administration of atogepant with the OATP inhibitor results in an increase in atogepant C max in the patient of about 2.2-fold relative to administration of atogepant alone.
8. 8 . The method according to claim 6 , wherein co-administration of atogepant with the OATP inhibitor results in an increase in atogepant AUC in the patient of about 2.8-fold relative to administration of atogepant alone.
9. 9 . The method according to claim 6 , wherein the OATP inhibitor is rifampin.
10. 10 . The method according to claim 6 , wherein the migraine is episodic migraine.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. application Ser. No. 17/953,536, filed Sep. 27, 2022; which claims the benefit of priority to U.S. Provisional Application No. 63/261,731, filed Sep. 27, 2021; U.S. Provisional Application No. 63/261,782, filed Sep. 28, 2021; U.S. Provisional Application No. 63/261,783, filed Sep. 28, 2021; U.S. Provisional Application No. 63/336,843, filed Apr. 29, 2022; and U.S. Provisional Application No. 63/395,134, filed Aug. 4, 2022. The entire contents of each of these applications is incorporated herein by reference in its entirety. FIELD The present disclosure is related to medicaments and methods for treating migraine. BACKGROUND Migraine is a highly prevalent, severe, and disabling neurological condition with a significant unmet need for effective treatments. (Holland, P. R. & Goadsby, P. J. Neurotherapeutics (2018). Migraine affects over 1 billion people worldwide, and it was reported as the second leading cause of disability in the 2016 Global Burden of Discase study. See GBD 2019 Diseases and Injuries Collaborators. Global Burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systemic analysis for the Global Burden of Disease Study 2019, Lancet 2020; 396:1204-22. When attacks are frequent or disabling, prevention becomes a focus of migraine treatment. Current preventive treatments for migraine include oral medications, such as valproic acid, flunarizine, topiramate, and propranolol, as well as injectable treatments, such as monoclonal antibodies targeting calcitonin gene-related peptide (CGRP). There remains a need for targeted methodologies and dosing regimens to use oral CGRP treatments to prophylactically treat migraines. SUMMARY In embodiments, the present disclosure provides methods for the preventive treatment of migraine in a patient, wherein the patient is undergoing concurrent treatment with a strong CYP3A4 inhibitor, the method comprising administering atogepant 10 mg once daily. In embodiments, the present disclosure provides methods for the preventive treatment of migraine in a patient, wherein the patient is undergoing concurrent treatment with a moderate or strong CYP3A4 inducer, the method comprising administering 30 mg or 60 mg atogepant once daily. In embodiments, the present disclosure provides methods for the preventive treatment of migraine in a patient, wherein the patient is undergoing concurrent treatment with an OATP inhibitor, the method comprising administering 10 mg or 30 mg atogepant once daily. In embodiments, the present disclosure provides methods for the preventive treatment of migraine in a patient, wherein the patient has severe renal impairment or end-stage renal disease (CLcr<30 mL/min), the method comprising administering 10 mg atogepant once daily. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 shows the mean plasma atogepant concentration-time profiles following administration of atogepant alone or in combination with single-dose rifampin to Fasted Healthy Participants. FIG. 2 shows the mean plasma atogepant concentration-time profiles following oral administration of atogepant alone or in combination with multiple-dose rifampin to Fasted Healthy Participants. FIG. 3 shows the mean plasma concentrations of atogepant after the administration of 60 mg either alone or in the presence of steady state itraconazole, a strong CYP3A4 inhibitor. FIG. 4 shows a semilogarithmic plot of the mean plasma concentrations of atogepant 60 mg either alone or in the presence of steady state itraconazole. FIG. 5A shows the mean plasma atogepant concentration-time profiles (linear scale) following single dose oral administration of 60 mg atogepant in participants with mild, moderate, or severe hepatic impairment and in participants with normal hepatic function (N=8 in each group). FIG. 5B shows a corresponding semi-logarithmic plot. FIG. 5A presents a full profile up to 72 hours, while 5B shows a truncated profile up to 8 hours. FIG. 6 shows the mean change from baseline in monthly migraine days in Study 1 (NCT03777059). FIG. 7 shows the distribution of change from baseline in mean monthly migraine days (MMD) across the 12-week treatment period, in 2-day increments, by treatment group in Study 1. FIG. 8 shows the mean change from baseline in MMD in Study 2 (NCT02848326). FIG. 9 shows the distribution of change from baseline in mean MMD across the 12-week treatment period, in 2-day increments, by treatment group in Study 2. A treatment benefit over placebo for all doses of atogepant is seen across a range of mean changes from baseline in MMD. FIG. 10 provides the mean concentration-time profiles for plasma atogepant after single dose administration of a 1×60 mg atogepant IR tablet formulation under fed conditions and under fasted conditions (linear scale±SD, with semilogarithmic scale insert). FIG. 11 provides boxplots of AUC0-t and AUC0-inf after single dose administration of a 1×60 mg atogep