Study to Assess Adverse Events When Ubrogepant Tablets in Combination With Atogepant Tablets Are Used to Treat Adult Participants With Migraine

• Atogepant (Drug), also known as QULIPTA: Oral Tablet
• Ubrogepant (Drug), also known as UBRELVY: Oral Tablet

Primary outcomes

• Number of Participants With Adverse Events (AEs) [From first dose of study drug until 30 days following last dose of study drug (up to approximately 28 weeks)]: An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. A treatment-emergent adverse event (TEAE) is an AE that occurs or worsens after receiving investigational study drug.
• Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator [Up to approximately 28 weeks]: Clinical laboratory test values are considered PCS if they meet either the lower-limit or higher-limit PCS criteria defined in the categories below. Percentage of participants with PCS laboratory values are summarized for chemistry, hematology, and urinalysis. Only those categories where at least 1 person had a non-PCS value at Baseline and met the PCS criterion at least once during post-baseline are reported.
• Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator [Up to approximately 24 weeks]: 12-lead ECGs were performed at select study visits. Only those categories where at least 1 person had a non-PCS value at Baseline and met the PCS criterion at least once during postbaseline are reported.
• Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator [Up to approximately 28 weeks]: PCS postbaseline vital sign values are summarized for categories: systolic and diastolic blood pressures \[sitting and standing\], pulse rate \[sitting and standing\], respiratory rate, temperature, weight. Only those categories where at least 1 person had a non-PCS value at Baseline and met the PCS criterion at least once during postbaseline are reported.
• Number of Participants With Suicidal Ideation and Behaviour Using 5-Point Scale of Columbia-Suicide Severity Rating Scale (C-SSRS) During the Open-Label Treatment Period [Week 1 to Week 12 for Safety Population 1; Week 12 to Week 24 for Safety Population 2]: C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and suicidal behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. Suicidal ideation: Minimum total score 1, maximum total score 5; higher total scores indicate more suicidal ideation. Suicidal behavior: Minimum total score 0, maximum total score 4; higher total scores indicate more suicidal behavior.
• Number of Participants With Suicidal Ideation and Behaviour Using 5-Point Scale of Columbia-Suicide Severity Rating Scale (C-SSRS) During the 4-Week Safety Follow-Up Period [From last dose of study drug to 4 weeks after last dose of study drug. Overall median time on atogepant treatment was 85 days.]: C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and suicidal behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. Suicidal ideation: Minimum total score 1, maximum total score 5; higher total scores indicate more suicidal ideation. Suicidal behavior: Minimum total score 0, maximum total score 4; higher total scores indicate more suicidal behavior.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* At least 1-year history of migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders (ICHD)-3, 2018.
* History of 4 to 14 migraine days per month on average in the 3 months prior to Screening (Visit 1) in the investigator's judgment.

Exclusion Criteria:

\- Clinically significant hematologic, endocrine, cardiovascular, cerebrovascular, pulmonary, renal, hepatic, gastrointestinal, or neurologic disease.

Participant flow

Outcome results

• Number of Participants With Adverse Events (AEs) (Primary), Count of participants, Participants: Atogepant 60 mg (Period 1) 130; Atogepant 60 mg + Ubrogepant 100 mg (Period 2) 94
• Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator (Primary), Number, participants: Atogepant 60 mg (Period 1) 3; Atogepant 60 mg + Ubrogepant 100 mg (Period 2) 3
• Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator (Primary), Number, participants: Atogepant 60 mg (Period 1) 0; Atogepant 60 mg + Ubrogepant 100 mg (Period 2) 0
• Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator (Primary), Number, participants: Atogepant 60 mg (Period 1) 4; Atogepant 60 mg + Ubrogepant 100 mg (Period 2) 2
• Number of Participants With Suicidal Ideation and Behaviour Using 5-Point Scale of Columbia-Suicide Severity Rating Scale (C-SSRS) During the Open-Label Treatment Period (Primary), Number, participants: Atogepant 60 mg (Period 1) 0; Atogepant 60 mg + Ubrogepant 100 mg (Period 2) 2
• Number of Participants With Suicidal Ideation and Behaviour Using 5-Point Scale of Columbia-Suicide Severity Rating Scale (C-SSRS) During the 4-Week Safety Follow-Up Period (Primary), Number, participants: Atogepant 60 mg (Period 1) 1

Adverse events

Time frame: All-cause mortality and adverse event tables include events reported from the time of informed consent to the end of the study. The median time on follow-up was 75.5 days from Visit 1 (Week -1) through end of Period 1 and 206 days from baseline through end of Period 2.

Serious adverse events by term

Other adverse events by term

• Results publication: Ailani J, Lipton RB, Blumenfeld AM, Mechtler L, Klein BC, He MY, Smith JH, Trugman JM, de Abreu Ferreira R, Brand-Schieber E. Safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the preventive treatment of episodic migraine: Results from the TANDEM study. Headache. 2025 Jun;65(6):1005-1014. doi: 10.1111/head.14871. Epub 2024 Nov 21. PMID 39569702

• Study Protocol (PDF, 2022-07-22)
• Statistical Analysis Plan (PDF, 2022-12-07)

• ABBVIE INC., Study director, AbbVie