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

Primary Purpose

Migraine

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ubrogepant

Erenumab

Galcanezumab

About this trial

This is an interventional basic science trial for Migraine focused on measuring ubrogepant, erenumab, galcanezumab, safety, tolerability, interaction

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

QPS
Spaulding

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part 1 (Intervention A then B then D)

Part 2 (Intervention A then C then D)

Arm Description

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 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.

Outcomes

Primary Outcome Measures

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

Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab

Part 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) for Ubrogepant Alone and in Combination With Erenumab

Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab

Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab

Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab

Secondary Outcome Measures

Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab

Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab

Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab

Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab

Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab

Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab

Part 1: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for Ubrogepant Alone and in Combination With Erenumab

Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab

Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab

Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab

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).

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

Number of Participants Who Had PCS Postbaseline Physical Examination Values

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.

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).

Full Information

NCT ID

NCT04179474

First Posted

September 26, 2019

Last Updated

February 17, 2021

Sponsor

Allergan

1. Study Identification

Unique Protocol Identification Number

NCT04179474

Brief Title

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

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

September 26, 2019 (Actual)

Primary Completion Date

December 23, 2019 (Actual)

Study Completion Date

December 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Allergan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Migraine

Keywords

ubrogepant, erenumab, galcanezumab, safety, tolerability, interaction

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 (Intervention A then B then D)

Arm Type

Experimental

Arm Description

Arm Title

Part 2 (Intervention A then C then D)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ubrogepant

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Erenumab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Galcanezumab

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Title

Part 2: AUC0-t for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Title

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

Title

Part 2: AUC0-∞ for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Title

Part 1: Maximum Plasma Drug Concentration (Cmax) for Ubrogepant Alone in Combination With Erenumab

Time Frame

Title

Part 2: Cmax for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Secondary Outcome Measure Information:

Title

Part 1: Time of Maximum Plasma Drug Concentration (Tmax) for Ubrogepant Alone and in Combination With Erenumab

Time Frame

Title

Part 2: Tmax for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Title

Part 1: Terminal Elimination Rate Constant (λz) for Ubrogepant Alone and in Combination With Erenumab

Time Frame

Title

Part 2: λz for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Title

Part 1: Terminal Elimination Half-life (T½) for Ubrogepant Alone and in Combination With Erenumab

Time Frame

Title

Part 2: T½ for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Title

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

Title

Part 2: CL/F for Ubrogepant Alone and in Combination With Galcanezumab

Time Frame

Title

Part 1: Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for Ubrogepant Alone in Combination With Erenumab

Time Frame

Title

Part 2: Vz/F for Ubrogepant Alone in Combination With Galcanezumab

Time Frame

Title

Number of Participants Who Had Potentially Clinically Significant (PCS) Postbaseline Vital Sign Values

Description

Time Frame

End of Dosing (EOD): Within 7 days of Day 16 or at the time of early termination (Up to Day 16)

Title

Number of Participants Who Had PCS Postbaseline Laboratory Values

Description

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)

Title

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)

Title

Number of Participants Who Had PCS Postbaseline Electrocardiogram (ECG) Values

Description

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.

Time Frame

EOD: Within 7 days of Day 16 or at the time of early termination (Up to Day 16)

Title

Number of Participants With Adverse Events (AEs) by Severity, Related AEs and AEs Leading to Discontinuation

Description

Time Frame

First dose to within 30 days after last dose (Up to Day 45 +/-3 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ramesh Boinpally

Organizational Affiliation

Allergan

Official's Role

Study Director

Facility Information:

Facility Name

QPS

City

Springfield

State/Province

Missouri

ZIP/Postal Code

65802

Country

United States

Facility Name

Spaulding

City

West Bend

State/Province

Wisconsin

ZIP/Postal Code

53095

Country

United States

12. IPD Sharing Statement

Citations:

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.

Results Reference

result

Learn more about this trial

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

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