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
Overview
- Phase
- Phase 1
- Intervention
- Ubrogepant
- Conditions
- Migraine
- Sponsor
- Allergan
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
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
Arms & Interventions
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.
Intervention: Ubrogepant
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.
Intervention: Erenumab
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.
Intervention: Ubrogepant
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.
Intervention: Galcanezumab
Outcomes
Primary Outcomes
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
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
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
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
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
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
Secondary Outcomes
- 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: 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: 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)
- 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))
- 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)
- 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))
- 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 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: 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)
- 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))
- 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))
- 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: 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 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))