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

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ClinicalTrials.gov Identifier: NCT04179474
Recruitment Status : Completed
First Posted : November 27, 2019
Results First Posted : March 10, 2021
Last Update Posted : March 10, 2021
Sponsor:
Information provided by (Responsible Party):
Allergan

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.

Condition or disease Intervention/treatment Phase
Migraine Drug: Ubrogepant Drug: Erenumab Drug: Galcanezumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : September 26, 2019
Actual Primary Completion Date : December 23, 2019
Actual Study Completion Date : December 23, 2019

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Migraine

Arm Intervention/treatment
Experimental: 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.
Drug: Ubrogepant
Oral administration of 100 mg ubrogepant tablet once daily [Intervention A=single dose and Intervention D=repeated daily dose].

Drug: Erenumab
Single dose subcutaneous (SC) injection of erenumab 140 mg [Intervention B].

Experimental: 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.
Drug: Ubrogepant
Oral administration of 100 mg ubrogepant tablet once daily [Intervention A=single dose and Intervention D=repeated daily dose].

Drug: Galcanezumab
2 SC injections of galcanezumab 120 mg [Intervention C].




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values [ Time Frame: 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).

  12. Number of Participants Who Had PCS Postbaseline Laboratory Values [ 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) ]
    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

  13. 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) ]
  14. Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values [ Time Frame: 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.

  15. Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation [ Time Frame: 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).



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04179474


Locations
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United States, Missouri
QPS
Springfield, Missouri, United States, 65802
United States, Wisconsin
Spaulding
West Bend, Wisconsin, United States, 53095
Sponsors and Collaborators
Allergan
Investigators
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Study Director: Ramesh Boinpally Allergan
  Study Documents (Full-Text)

Documents provided by Allergan:
Statistical Analysis Plan  [PDF] March 18, 2020
Study Protocol  [PDF] August 14, 2019

Publications of Results:
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.

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Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT04179474    
Other Study ID Numbers: 3110-108-002
First Posted: November 27, 2019    Key Record Dates
Results First Posted: March 10, 2021
Last Update Posted: March 10, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Allergan:
ubrogepant
erenumab
galcanezumab
safety
tolerability
interaction
Additional relevant MeSH terms:
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Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Erenumab
Calcitonin Gene-Related Peptide Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs