Episodic Migraine
Conditions
Keywords
Episodic Migraine, Ubrogepant, Atogepant, QULIPTA, UBRELVY
Brief summary
Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound. This study will assess the safety and efficacy of the combination use of ubrogepant for the acute treatment of migraine headache in participants taking atogepant once daily for preventive treatment of migraine. Ubrogepant is an approved drug for the acute treatment of migraine. Atogepant is an approved drug for the preventive treatment of migraine. Approximately 235 adult participants with EM will be enrolled in approximately 45 sites in the United States. Participants will receive oral atogepant tablets once daily (QD) for 12 weeks followed by continued atogepant treatment with ubrogepant tablets taken as needed for the next 12 weeks. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGAtogepant
Oral Tablet
DRUGUbrogepant
Oral Tablet
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 263 participants were enrolled and included in the intent-to-treat (ITT) population; 1 participant withdrew consent before receiving study drug and therefore was not included in the demographics or any analyses.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Participants will receive atogepant 60 mg tablets orally once daily for 12 weeks (Day 1 to Week 12) in Period 1 then atogepant 60 mg tablets orally once daily and ubrogepant 100 mg tablets orally as needed for an additional 12 weeks (Week 12 to Week 24) in Period 2. | 262 |
| Total | 262 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Customized Age Group 20 to 29 years | 43 Participants |
| Age, Customized Age Group < 20 years | 0 Participants |
| Age, Customized Age Group 30 to 39 years | 60 Participants |
| Age, Customized Age Group 40 to 49 years | 71 Participants |
| Age, Customized Age Group 50 to 59 years | 53 Participants |
| Age, Customized Age Group 60 to 69 years | 33 Participants |
| Age, Customized Age Group ≥ 70 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 235 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 44 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 205 Participants |
| Sex: Female, Male Female | 214 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 263 | 0 / 218 |
| other Total, other adverse events | 66 / 263 | 15 / 218 |
| serious Total, serious adverse events | 1 / 263 | 1 / 218 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
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.
Time frame: From first dose of study drug until 30 days following last dose of study drug (up to approximately 28 weeks)
Population: Safety Population 1 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant treatment period) and Safety Population 2 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant + ubrogepant concomitant-use treatment period).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atogepant 60 mg (Period 1) | Number of Participants With Adverse Events (AEs) | 130 Participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Number of Participants With Adverse Events (AEs) | 94 Participants |
Primary
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
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.
Time frame: From last dose of study drug to 4 weeks after last dose of study drug. Overall median time on atogepant treatment was 85 days.
Population: Safety Population 1 consisted of all subjects who received at least 1 dose of study drug during the open-label atogepant treatment period. The statistical analysis plan (SAP) does not include the Safety Population 2 (all subjects who received at least 1 dose of study drug in Period 2) subgroup analyses for this primary outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atogepant 60 mg (Period 1) | 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 | Suicidal Ideation During Follow-Up Period | 1 participants |
| Atogepant 60 mg (Period 1) | 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 | Suicidal Behavior During Follow-Up Period | 0 participants |
Primary
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
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.
Time frame: Week 1 to Week 12 for Safety Population 1; Week 12 to Week 24 for Safety Population 2
Population: Safety Population 1 consisted of all subjects who received at least 1 dose of study drug during the open-label atogepant treatment period as well as Safety Population 2 consisted of all subjects who went on to receive at least 1 dose of study drug during the open-label atogepant + ubrogepant concomitant-use treatment period.~The one subject with positive suicidal behavior was erroneously reported in the questionnaire and had not had a positive suicidal behavior throughout the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atogepant 60 mg (Period 1) | 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 | Suicidal Ideation | 0 participants |
| Atogepant 60 mg (Period 1) | 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 | Suicidal Behavior | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 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 | Suicidal Ideation | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 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 | Suicidal Behavior | 1 participants |
Primary
Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator
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.
Time frame: Up to approximately 24 weeks
Population: Safety Population 1 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant treatment period) and Safety Population 2 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant + ubrogepant concomitant-use treatment period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | PR Interval (msec): ≥ 250 | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QRS Interval (msec): ≥ 150 | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcB (msec): > 500 | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcB (msec): Increase of > 60 | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcF (msec): > 500 | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcF (msec): Increase of > 60 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcF (msec): > 500 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | PR Interval (msec): ≥ 250 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcB (msec): Increase of > 60 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QRS Interval (msec): ≥ 150 | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcF (msec): Increase of > 60 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator | QTcB (msec): > 500 | 0 participants |
Primary
Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator
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.
Time frame: Up to approximately 28 weeks
Population: Safety Population 1 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant treatment period) and Safety Population 2 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant + ubrogepant concomitant-use treatment period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Bilirubin, Chemistry (µmol/L): ≥ 1.5 * ULN | 2 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Hematocrit (fraction of 1): < 0.9 * LLN | 5 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Calcium (mmol/L): < 0.9 * LLN | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Lymphocytes (10^9/L): > 1.3 * ULN | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Creatine Kinase (U/L): > 2.0 * ULN | 9 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Glucose, Chemistry (mmol/L): > 2.0 * ULN | 2 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Glucose, Chemistry (mmol/L): < 0.8 * LLN | 2 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Neutrophils (10^9/L): < 0.7 * LLN | 4 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Neutrophils (10^9/L): > 1.3 * ULN | 4 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Lactate Dehydrogenase (U/L): > 3.0 * ULN | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Hemoglobin (g/L): < 0.9 * LLN | 6 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Phosphate (mmol/L): < 0.9 * LLN | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Platelets (10^9/L): < 0.5 * LLN | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Phosphate (mmol/L): > 1.1 * ULN | 3 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Erythrocytes, Hematology (10^12/L): < 0.9 * LLN | 3 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Potassium (mmol/L): < 0.9 * LLN | 0 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Alanine Aminotransferase (U/L): ≥ 3.0 * ULN | 3 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Potassium (mmol/L): > 1.1 * ULN | 5 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Leukocytes, Hematology (10^9/L): < 0.9 * LLN | 3 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Protein, Chemistry (g/L): < 0.9 * LLN | 3 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Aspartate Aminotransferase (U/L): ≥ 3.0 * ULN | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Glucose, Urinalysis: At least 1+ | 4 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Bicarbonate (mmol/L): < 0.9 * LLN | 5 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Protein, Urinalysis: At least 1+ | 38 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Lymphocytes (10^9/L): < 0.7 * LLN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Protein, Urinalysis: At least 1+ | 39 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Erythrocytes, Hematology (10^12/L): < 0.9 * LLN | 3 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Hematocrit (fraction of 1): < 0.9 * LLN | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Hemoglobin (g/L): < 0.9 * LLN | 3 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Leukocytes, Hematology (10^9/L): < 0.9 * LLN | 7 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Lymphocytes (10^9/L): < 0.7 * LLN | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Lymphocytes (10^9/L): > 1.3 * ULN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Neutrophils (10^9/L): > 1.3 * ULN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Platelets (10^9/L): < 0.5 * LLN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Alanine Aminotransferase (U/L): ≥ 3.0 * ULN | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Aspartate Aminotransferase (U/L): ≥ 3.0 * ULN | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Bicarbonate (mmol/L): < 0.9 * LLN | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Bilirubin, Chemistry (µmol/L): ≥ 1.5 * ULN | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Calcium (mmol/L): < 0.9 * LLN | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Creatine Kinase (U/L): > 2.0 * ULN | 5 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Glucose, Chemistry (mmol/L): < 0.8 * LLN | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Glucose, Chemistry (mmol/L): > 2.0 * ULN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Lactate Dehydrogenase (U/L): > 3.0 * ULN | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Phosphate (mmol/L): < 0.9 * LLN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Phosphate (mmol/L): > 1.1 * ULN | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Potassium (mmol/L): < 0.9 * LLN | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Potassium (mmol/L): > 1.1 * ULN | 4 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Protein, Chemistry (g/L): < 0.9 * LLN | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Glucose, Urinalysis: At least 1+ | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values as Assessed by the Investigator | Neutrophils (10^9/L): < 0.7 * LLN | 1 participants |
Primary
Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator
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.
Time frame: Up to approximately 28 weeks
Population: Safety Population 1 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant treatment period) and Safety Population 2 (all subjects who received ≥ 1 dose of study drug during the open-label atogepant + ubrogepant concomitant-use treatment period).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Orthostatic Systolic Blood Pressure (mmHg): ≤ -20 | 12 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Pulse Rate (bpm): ≤ 50 and Decrease of ≥ 15 | 4 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 2 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Pulse Rate (bpm): ≥ 120 and Increase of ≥ 15 | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 4 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Pulse Rate (bpm): ≤ 50 and Decrease of ≥ 15 | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Diastolic Blood Pressure (mmHg): ≥ 105 and Increase of ≥ 15 | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Weight (kg): Increase of ≥ 7% | 5 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Weight (kg): Decrease of ≥ 7% | 16 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Diastolic Blood Pressure (mmHg): ≥ 105 and Increase of ≥ 15 | 5 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Systolic Blood Pressure (mmHg): ≥ 180 and Increase of ≥ 20 | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Orthostatic Diastolic Blood Pressure (mmHg): ≤ -15 | 6 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Diastolic Blood Pressure (mmHg): ≤ 50 and Decrease of ≥ 15 | 1 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Orthostatic Pulse Rate (bpm): ≥ 25 | 10 participants |
| Atogepant 60 mg (Period 1) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Pulse Rate (bpm): ≥ 120 and Increase of ≥ 15 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Orthostatic Pulse Rate (bpm): ≥ 25 | 7 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Systolic Blood Pressure (mmHg): ≥ 180 and Increase of ≥ 20 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Systolic Blood Pressure (mmHg): ≤ 90 and Decrease of ≥ 20 | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Diastolic Blood Pressure (mmHg): ≥ 105 and Increase of ≥ 15 | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Diastolic Blood Pressure (mmHg): ≥ 105 and Increase of ≥ 15 | 3 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Pulse Rate (bpm): ≥ 120 and Increase of ≥ 15 | 1 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Sitting Pulse Rate (bpm): ≤ 50 and Decrease of ≥ 15 | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Pulse Rate (bpm): ≥ 120 and Increase of ≥ 15 | 2 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Pulse Rate (bpm): ≤ 50 and Decrease of ≥ 15 | 0 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Weight (kg): Increase of ≥ 7% | 7 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Weight (kg): Decrease of ≥ 7% | 28 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Orthostatic Systolic Blood Pressure (mmHg): ≤ -20 | 7 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Orthostatic Diastolic Blood Pressure (mmHg): ≤ -15 | 10 participants |
| Atogepant 60 mg + Ubrogepant 100 mg (Period 2) | Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator | Standing Diastolic Blood Pressure (mmHg): ≤ 50 and Decrease of ≥ 15 | 1 participants |