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

NCT04179474 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 3110-108-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Migraine

Keywords

ubrogepant; erenumab; galcanezumab; safety; tolerability; interaction

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (15)

• 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

Study Arms (2)

Part 1 (Intervention A then B then D)

EXPERIMENTAL

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; Drug: Erenumab

Part 2 (Intervention A then C then D)

EXPERIMENTAL

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; Drug: Galcanezumab

Interventions

Ubrogepant DRUG

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

Part 1 (Intervention A then B then D); Part 2 (Intervention A then C then D)

Erenumab DRUG

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

Part 1 (Intervention A then B then D)

Galcanezumab DRUG

2 SC injections of galcanezumab 120 mg \[Intervention C\].

Part 2 (Intervention A then C then D)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Allergan: lead

Study Sites (2)

QPS

Springfield, Missouri, 65802, United States

Location

Spaulding

West Bend, Wisconsin, 53095, United States

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Migraine Disorders

Interventions

ubrogepant; erenumab; galcanezumab

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Ramesh Boinpally

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: November 27, 2019
• Study Start: September 26, 2019
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: March 10, 2021
• Results First Posted: March 10, 2021

Record last verified: 2021-02

Locations

US (2)