Migraine
Conditions
Keywords
ubrogepant, erenumab, galcanezumab, safety, tolerability, interaction
Brief summary
This study will evaluate the potential for a pharmacokinetic (PK) interaction and provide safety and tolerability information when ubrogepant and erenumab or ubrogepant and galcanezumab are co-administered.
Interventions
DRUGUbrogepant
Oral administration of 100 mg ubrogepant tablet once daily \[Intervention A=single dose and Intervention D=repeated daily dose\].
DRUGErenumab
Single dose subcutaneous (SC) injection of erenumab 140 mg \[Intervention B\].
DRUGGalcanezumab
2 SC injections of galcanezumab 120 mg \[Intervention C\].
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* At least a 1-year history of migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd edition, (ICHD-3, 2018) * By history, the participant's migraines typically last between 4 and 72 hours if untreated or treated unsuccessfully and migraine episodes are separated by at least 48 hours of headache pain freedom * History of at least 2 migraine attacks per month in the 2 months prior to Screening * Have a sitting pulse rate ≥ 45 beats per minute (bpm) and ≤ 100 bpm during the vital sign assessment at the Screening Visit. Clinical site may perform a maximum of 2 repeats of vital sign measurements if the initial measurement is out of range. * Negative test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, cannabinoids, opiates, and phencyclidine at the Screening Visit and Day -1; unless explained by concomitant medication use (eg, opioids prescribed for migraine pain) * Participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period
Exclusion criteria
* Difficulty distinguishing migraine headache from tension-type or other headaches * Has a history of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine as defined by ICHD-3 * Has a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy as defined by ICHD-3 * Required hospital treatment of a migraine attack 3 or more times in the 6 months prior to Screening * Has a chronic non-headache pain condition requiring daily pain medication (with the exception of pregabalin) * Has clinically significant cardiovascular or cerebrovascular disease per the investigator's opinion * Previously participated in an investigational study of ubrogepant * Participation in any other clinical investigation using an experimental drug within 30 days prior to study intervention administration * Participation in a blood or plasma donation program within 60 or 30 days, respectively, prior to study intervention administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time t (AUC0-t) for Ubrogepant Alone and in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose |
| Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose |
| Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) for Ubrogepant Alone and in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose |
| Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose |
| Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose |
| Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Number of Participants Who Had PCS Postbaseline Laboratory Values | EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16); Follow-up Visit 30 days after last dose (Up to Day 45 +/-3 days) | Laboratory assessments included Chemistry, Hematology and Urinalysis tests. The investigator determined if the postbaseline laboratory results were potentially clinically significant using the Clinical Laboratory PCS Criteria in the SAP. Assessments of Chemistry only were collected at the Final Follow-up Visit |
| Number of Participants Who Had PCS Postbaseline Physical Examination Values | EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16) | — |
| Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values | EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16) | A standard 12-lead ECG was performed. The investigator determined if the ECG postbaseline values were potentially clinically significant using the ECG PCS Criteria in the SAP. |
| Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | First dose to within 30 days after last dose (Up to Day 45 +/-3 days) | An AE is any untoward medical occurrence in a patient or a participant using an investigational drug, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The investigator determined if the AE was causally related to treatment. The investigator determined if the severity of the AE was Mild (transient with minimal intervention that does not interfere with usual activities), Moderate ( usually alleviated with an intervention, interferes with usual activities causing discomfort but does not cause permanent harm) or Severe (interrupts usual activities, affects clinical status or requires intensive intervention). |
| Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values | End of Dosing (EOD): Within 7 days of Day 16 or at the time of early termination (Up to Day 16) | Vital Signs included assessments of Blood Pressure, Pulse Rate, Weight, Respiratory Rate and Temperature. The investigator determined if the postbaseline Vital Sign values were potentially clinically significant using the Vital Sign PCS Criteria in the Statistical Analysis Plan (SAP). |
| Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
| Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab | Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (Intervention A Then B Then D) Intervention A: Single oral dose of ubrogepant 100 mg tablet on Day 1 under fasted conditions; followed by Intervention B: Single subcutaneous (SC) injection of erenumab 140 mg on Day 8; followed by Intervention D: Ubrogepant 100 mg tablet orally once daily on Days 12, 13, 14 and 15 under fasted conditions. | 20 |
| Part 2 (Intervention A Then C Then D) Intervention A: Single oral dose of ubrogepant 100 mg tablet on Day 1 under fasted conditions; followed by Intervention C: Two SC injections of galcanezumab 120 mg on Day 8; followed by Intervention D: Ubrogepant 100 mg tablet orally once daily on Days 12, 13, 14 and 15 under fasted conditions. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Part 1 (Intervention A Then B Then D) | Total | Part 2 (Intervention A Then C Then D) |
|---|---|---|---|
| Age, Customized | 32.2 years | 35.3 years | 38.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 36 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 16 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 23 Participants | 11 Participants |
| Region of Enrollment North America | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Female | 10 Participants | 22 Participants | 12 Participants |
| Sex: Female, Male Male | 10 Participants | 18 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 7 / 20 | 8 / 19 | 7 / 19 | 2 / 20 | 3 / 20 | 4 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 | 0 / 19 | 0 / 20 | 0 / 20 | 0 / 19 |
Outcome results
Primary
Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) for Ubrogepant Alone and in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) for Ubrogepant Alone and in Combination With Erenumab | 1878.25 ng*h/mL | Standard Deviation 497.82 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) for Ubrogepant Alone and in Combination With Erenumab | 1993.40 ng*h/mL | Standard Deviation 639.22 |
Comparison: A linear mixed-effects model with study intervention as fixed effect and participant as a random effect was used to determine the Geometric Means.90% CI: [96.19, 115.45]
Primary
Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time t (AUC0-t) for Ubrogepant Alone and in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: Pharmacokinetic 1 (PK1) population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time t (AUC0-t) for Ubrogepant Alone and in Combination With Erenumab | 1841.42 nanogram*hour/milliliter (ng*h/mL) | Standard Deviation 490.17 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time t (AUC0-t) for Ubrogepant Alone and in Combination With Erenumab | 1959.96 nanogram*hour/milliliter (ng*h/mL) | Standard Deviation 639.51 |
Comparison: A linear mixed-effects model with study intervention as fixed effect and participant as a random effect was used to determine the Geometric Means.90% CI: [96.21, 115.79]
Primary
Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab | 459.32 ng/mL | Standard Deviation 168.56 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab | 486.80 ng/mL | Standard Deviation 201.52 |
Comparison: A linear mixed-effects model with study intervention as fixed effect and participant as a random effect was used to determine the Geometric Means90% CI: [93.01, 115.98]
Primary
Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab | 1732.22 ng*h/mL | Standard Deviation 928.06 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab | 1793.74 ng*h/mL | Standard Deviation 1057.02 |
Comparison: A linear mixed-effects model with study intervention as fixed effect and participant as a random effect was used to determine the Geometric Means.90% CI: [89.68, 122.38]
Primary
Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab | 1700.31 ng*h/mL | Standard Deviation 913.42 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab | 1758.05 ng*h/mL | Standard Deviation 1033.44 |
Comparison: A linear mixed-effects model with study intervention as fixed effect and participant as a random effect was used to determine the Geometric Means.90% CI: [89.55, 123.19]
Primary
Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab | 415.34 ng/mL | Standard Deviation 225.64 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab | 375.12 ng/mL | Standard Deviation 152.08 |
Comparison: A linear mixed-effects model with study intervention as fixed effect and participant as a random effect was used to determine the Geometric Means.90% CI: [82.27, 120.45]
Secondary
Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values
A standard 12-lead ECG was performed. The investigator determined if the ECG postbaseline values were potentially clinically significant using the ECG PCS Criteria in the SAP.
Time frame: EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16)
Population: Safety population included all participants who received/took at least 1 administration of study intervention in Part 1 or Part 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ubrogepant Alone | Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values | 0 Participants |
Secondary
Number of Participants Who Had PCS Postbaseline Laboratory Values
Laboratory assessments included Chemistry, Hematology and Urinalysis tests. The investigator determined if the postbaseline laboratory results were potentially clinically significant using the Clinical Laboratory PCS Criteria in the SAP. Assessments of Chemistry only were collected at the Final Follow-up Visit
Time frame: EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16); Follow-up Visit 30 days after last dose (Up to Day 45 +/-3 days)
Population: Safety population included all participants who received/took at least 1 administration of study intervention in Part 1 or Part 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Number of Participants Who Had PCS Postbaseline Laboratory Values | Hematology; EOD | 0 Participants |
| Part 1: Ubrogepant Alone | Number of Participants Who Had PCS Postbaseline Laboratory Values | Chemistry; EOD | 0 Participants |
| Part 1: Ubrogepant Alone | Number of Participants Who Had PCS Postbaseline Laboratory Values | Chemistry; Follow-up Visit | 1 Participants |
| Part 1: Ubrogepant Alone | Number of Participants Who Had PCS Postbaseline Laboratory Values | Urinalysis; EOD | 1 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants Who Had PCS Postbaseline Laboratory Values | Urinalysis; EOD | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants Who Had PCS Postbaseline Laboratory Values | Hematology; EOD | 1 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants Who Had PCS Postbaseline Laboratory Values | Chemistry; Follow-up Visit | 1 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants Who Had PCS Postbaseline Laboratory Values | Chemistry; EOD | 0 Participants |
Secondary
Number of Participants Who Had PCS Postbaseline Physical Examination Values
Time frame: EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16)
Population: As per the SAP, abnormalities in physical examinations during the study were captured in medical history or Adverse Events (AEs) data panels. Therefore, there were no separate analyses for physical examination planned.
Secondary
Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values
Vital Signs included assessments of Blood Pressure, Pulse Rate, Weight, Respiratory Rate and Temperature. The investigator determined if the postbaseline Vital Sign values were potentially clinically significant using the Vital Sign PCS Criteria in the Statistical Analysis Plan (SAP).
Time frame: End of Dosing (EOD): Within 7 days of Day 16 or at the time of early termination (Up to Day 16)
Population: Safety population included all participants who received/took at least 1 administration of study intervention in Part 1 or Part 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Ubrogepant Alone | Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values | 0 Participants |
Secondary
Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation
An AE is any untoward medical occurrence in a patient or a participant using an investigational drug, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The investigator determined if the AE was causally related to treatment. The investigator determined if the severity of the AE was Mild (transient with minimal intervention that does not interfere with usual activities), Moderate ( usually alleviated with an intervention, interferes with usual activities causing discomfort but does not cause permanent harm) or Severe (interrupts usual activities, affects clinical status or requires intensive intervention).
Time frame: First dose to within 30 days after last dose (Up to Day 45 +/-3 days)
Population: Safety population included all participants who received/took at least 1 administration of study intervention. Data is reported by intervention actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | All AEs | 7 Participants |
| Part 1: Ubrogepant Alone | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Mild | 7 Participants |
| Part 1: Ubrogepant Alone | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Moderate | 0 Participants |
| Part 1: Ubrogepant Alone | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Severe | 0 Participants |
| Part 1: Ubrogepant Alone | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | Related AEs | 2 Participants |
| Part 1: Ubrogepant Alone | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Mild | 8 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Severe | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | All AEs | 8 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Moderate | 0 Participants |
| Part 1: Ubrogepant in Combination With Erenumab | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | Related AEs | 7 Participants |
| Part 1: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Part 1: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | Related AEs | 5 Participants |
| Part 1: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Severe | 1 Participants |
| Part 1: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Moderate | 0 Participants |
| Part 1: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | All AEs | 7 Participants |
| Part 1: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Mild | 6 Participants |
| Part 2: Intervention A (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Severe | 0 Participants |
| Part 2: Intervention A (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Mild | 2 Participants |
| Part 2: Intervention A (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Moderate | 0 Participants |
| Part 2: Intervention A (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Part 2: Intervention A (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | Related AEs | 0 Participants |
| Part 2: Intervention A (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | All AEs | 2 Participants |
| Part 2: Intervention C (Galcanezumab) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | All AEs | 3 Participants |
| Part 2: Intervention C (Galcanezumab) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | Related AEs | 3 Participants |
| Part 2: Intervention C (Galcanezumab) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Mild | 3 Participants |
| Part 2: Intervention C (Galcanezumab) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Moderate | 0 Participants |
| Part 2: Intervention C (Galcanezumab) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Severe | 0 Participants |
| Part 2: Intervention C (Galcanezumab) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Part 2: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Severe | 0 Participants |
| Part 2: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Moderate | 0 Participants |
| Part 2: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | Related AEs | 3 Participants |
| Part 2: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Part 2: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | AEs by Severity: Mild | 4 Participants |
| Part 2: Intervention D (Ubrogepant) | Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation | All AEs | 4 Participants |
Secondary
Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab | 57.35 liter/hour | Standard Deviation 17.2 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab | 54.74 liter/hour | Standard Deviation 16.27 |
Secondary
Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab | 436.95 liter | Standard Deviation 158.11 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab | 375.84 liter | Standard Deviation 161.42 |
Secondary
Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab | 5.26 hour | Standard Deviation 1 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab | 4.62 hour | Standard Deviation 0.94 |
Secondary
Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab | 0.136 1/hour | Standard Deviation 0.025 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab | 0.156 1/hour | Standard Deviation 0.034 |
Secondary
Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Ubrogepant Alone | Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab | 1.50 hour |
| Part 1: Ubrogepant in Combination With Erenumab | Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab | 1.48 hour |
Secondary
Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab | 72.90 liter/hour | Standard Deviation 38.07 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab | 68.94 liter/hour | Standard Deviation 28.12 |
Secondary
Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab | 5.04 hour | Standard Deviation 1.47 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab | 4.60 hour | Standard Deviation 1.35 |
Secondary
Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab | 1.50 hour |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab | 1.50 hour |
Secondary
Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab | 568.66 liter | Standard Deviation 497.92 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab | 449.26 liter | Standard Deviation 213.84 |
Secondary
Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab
Time frame: Day 1 (Treatment Period 1): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose; Day 12 (Day 1 of Treatment Period 3): Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 14, and 24 hours postdose
Population: PK1 population included all participants who had evaluable plasma PK parameters of ubrogepant for both ubrogepant alone and ubrogepant in combination with erenumab or galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Ubrogepant Alone | Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab | 0.150 1/hour | Standard Deviation 0.053 |
| Part 1: Ubrogepant in Combination With Erenumab | Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab | 0.165 1/hour | Standard Deviation 0.056 |