Safety, Tolerability and Drug- Drug Interaction Study of Ubrogepant With Erenumab or Galcanezumab in Participants With Migraine

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1b, Two-Part, Open-Label, Fixed-Sequence, Safety, Tolerability and Drug-Drug Interaction Study Between Single Dose Erenumab or Galcanezumab and Multiple Dose Ubrogepant in Participants With Migraine

Conditions
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Migraine

Intervention / Treatment
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* Drug: Ubrogepant
* Drug: Erenumab
* Drug: Galcanezumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (Intervention A then B then D)<br>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. | Drug: Ubrogepant<br>* Oral administration of 100 mg ubrogepant tablet once daily [Intervention A=single dose and Intervention D=repeated daily dose].<br>Drug: Erenumab<br>* Single dose subcutaneous (SC) injection of erenumab 140 mg [Intervention B].<br>|
| Experimental: Part 2 (Intervention A then C then D)<br>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. | Drug: Ubrogepant<br>* Oral administration of 100 mg ubrogepant tablet once daily [Intervention A=single dose and Intervention D=repeated daily dose].<br>Drug: Galcanezumab<br>* 2 SC injections of galcanezumab 120 mg [Intervention C].<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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). | End of Dosing (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 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 | 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) | 
| 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 | 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. | EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16) | 
| 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). | First dose to within 30 days after last dose (Up to Day 45 +/-3 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ubrogepant, erenumab, galcanezumab, safety, tolerability, interaction