Clinical trial NCT04179474: Safety, Tolerability and Drug- Drug Interaction Study of Ubrogepant With Erenumab or Galcanezumab in Participants With Migraine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Migraine
Keywords: ubrogepant
erenumab
galcanezumab
safety
tolerability
interaction
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2019-11-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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
measure: Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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
measure: Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) for Ubrogepant Alone and in Combination With Erenumab
timeFrame: 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
measure: Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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
measure: Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab
timeFrame: 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
measure: Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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 outcomes:
measure: Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab
timeFrame: 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
measure: Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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
measure: Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab
timeFrame: 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
measure: Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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
measure: Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab
timeFrame: 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
measure: Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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
measure: Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab
timeFrame: 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
measure: Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab
timeFrame: 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
measure: Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab
timeFrame: 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
measure: Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab
timeFrame: 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
measure: Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values
timeFrame: End of Dosing (EOD): Within 7 days of Day 16 or at the time of early termination (Up to Day 16)
measure: Number of Participants Who Had PCS Postbaseline Laboratory Values
timeFrame: 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)
measure: Number of Participants Who Had PCS Postbaseline Physical Examination Values
timeFrame: EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16)
measure: Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values
timeFrame: EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16)
measure: Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation
timeFrame: First dose to within 30 days after last dose (Up to Day 45 +/-3 days)
Other outcomes:
Locations:
city: Springfield
country: United States
facility: QPS
state: Missouri
city: West Bend
country: United States
facility: Spaulding
state: Wisconsin
Study officials:
affiliation: Allergan
name: Ramesh Boinpally
role: STUDY_DIRECTOR
References:
citation: Jakate A,Boinpally R, Butler M, Borbridge L, Contreras-De Lama J, McGeeney D, Periclou A. Safety and tolerability of ubrogepant for the acute treatment of migraine following co-administration with preventive monoclonal antibody treatment [abstract]. In:62nd Annual Scientific Meeting American Headache Society; June2020; San Diego, California.