Clinical trial NCT02867709: Efficacy, Safety, and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled Single Attack Study to Evaluate the Efficacy, Safety, and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine, With or Without Aura
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2016-08-16
Enrollment: 1686
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, and tolerability of 2 doses of ubrogepant (25 and 50 mg) compared to placebo for the acute treatment of a single migraine attack.


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, beta version
* Migraine onset before age 50
* History of migraines typically lasting 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 2 to 8 migraine attacks per month with moderate to severe headache pain in each of the previous 3 months.

Exclusion Criteria:

* Difficulty distinguishing migraine headache from tension-type other headaches
* Has taken medication for acute treatment of headache (including acetaminophen, nonsteroidal anti-inflammatory drugs \[NSAIDs\], triptans, ergotamine, opioids, or combination analgesics) on 10 or more days per month in the previous 3 months
* Has a history of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine
* Has a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy
* Required hospital treatment of a migraine attack 3 or more times in the previous 6 months
* Has a chronic non-headache pain condition requiring daily pain medication
* Has a history of malignancy in the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
* Has a history of any prior gastrointestinal conditions (eg, diarrhoea syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of investigational product; participants with prior gastric bariatric interventions which have been reversed are not excluded
* Has a history of hepatitis within previous 6 months.

Primary outcomes:
measure: Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose
timeFrame: Baseline (Predose) to 2 hours after initial dose
measure: Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose
timeFrame: Baseline (Predose) to 2 hours after initial dose
Secondary outcomes:
measure: Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose
timeFrame: Baseline (Predose) to 2 hours after initial dose
measure: Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose
timeFrame: 2 to 24 hours after initial dose
measure: Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose
timeFrame: 2 to 24 hours after initial dose
measure: Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose
timeFrame: 2 hours after initial dose
measure: Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose
timeFrame: 2 hours after initial dose
measure: Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose
timeFrame: 2 hours after initial dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Advantage, Inc./Simon Williamson Clinic
state: Alabama
city: Chandler
country: United States
facility: Clinical Research Advantage, Inc./East Valley Family Physicians, PLC
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital & Medical Center - Barrow Neurologic Institute (BNI)
state: Arizona
city: Phoenix
country: United States
facility: Clinical Research Advantage, Inc./Central Phoenix Medical Clinic, LLC
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona, May Clinic Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Radiant Research Inc.
state: Arizona
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Apple Valley
country: United States
facility: Axiom Research, LLC
state: California
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Colton
country: United States
facility: Axiom Research, LLC
state: California
city: Encino
country: United States
facility: Pharmacology Research Institute
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Fresno
country: United States
facility: California Headache and Balance Center
state: California
city: Imperial
country: United States
facility: Sun Valley Research Center
state: California
city: La Mesa
country: United States
facility: Grossmont Center For Clinical Research
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Los Angeles
country: United States
facility: California Advanced Neurotherapeutic, Inc.
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Pain Center
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Rancho Cucamonga
country: United States
facility: Rancho Cucamonga Clinical Research
state: California
city: Rancho Mirage
country: United States
facility: Desert Valley Research
state: California
city: Redondo Beach
country: United States
facility: George J Rederich MD, Inc
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research
state: California
city: Vista
country: United States
facility: Clinical Research Advantage, Inc./Cassidy Medical Group-Vista
state: California
city: Colorado Springs
country: United States
facility: Clinicos, LLC
state: Colorado
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Fort Collins
country: United States
facility: Advanced Neurosciences Research, LLC
state: Colorado
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Radiant Clinical Research
state: District of Columbia
city: Aventura
country: United States
facility: Aventura Neurological Associates
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research South Florida
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Hollywood
country: United States
facility: Broward Research Group
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, P.A.
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: LCC Medical Research Institute, LLC
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research, Corp.
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare, LLC
state: Florida
city: South Miami
country: United States
facility: QPS MRA, LLC (Miami Research Associates)
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: The Kaufmann Clinic, Inc.
state: Georgia
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Chicago
country: United States
facility: Clinical Research Advantage, Inc./Michigan Avenue Internists
state: Illinois
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Riverwoods
country: United States
facility: Robbins Headache Clinic
state: Illinois
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology P.C.
state: Indiana
city: Louisville
country: United States
facility: Norton Neurology Services MS Services
state: Kentucky
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Baltimore
country: United States
facility: Seton Medical Group
state: Maryland
city: Baltimore
country: United States
facility: Overlea Personal Physicians
state: Maryland
city: New Bedford
country: United States
facility: BTC of New Bedford
state: Massachusetts
city: Quincy
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Worcester
country: United States
facility: New England Regional Headache Center, Inc.
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Ridgeland
country: United States
facility: The Headache Center
state: Mississippi
city: Fremont
country: United States
facility: Clinical Research Advantage, Inc./Prairie Fields Family Medicine, PC
state: Nebraska
city: Omaha
country: United States
facility: Clinical Research Advantage, Inc
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Hope Research Institute
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Skillman
country: United States
facility: Princeton Center for Clinical Research
state: New Jersey
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: Amherst
country: United States
facility: DENT Neurosciences Research Center
state: New York
city: Great Neck
country: United States
facility: Cushing Neuroscience Institute North Shore-LIJ Medical Group
state: New York
city: Plainview
country: United States
facility: ProHealth Care Associates, LLP
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates, LLC
state: New York
city: Yonkers
country: United States
facility: Westchester Neuro. Const
state: New York
city: Durham
country: United States
facility: Carolina Headache Institute
state: North Carolina
city: Greensboro
country: United States
facility: Headache Wellness Center, PC
state: North Carolina
city: Mooresville
country: United States
facility: Lake Shore Clinical Research, LLC
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates, PA
state: North Carolina
city: Fargo
country: United States
facility: Plains Clinical Research Center, LLC
state: North Dakota
city: Akron
country: United States
facility: Radiant Research, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Sentral Clinical Research Services
state: Ohio
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites, LLC
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Dept of Psychiatry & Behavioral Neuroscience
state: Ohio
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Inc.
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates, Ltd.
state: Pennsylvania
city: Anderson
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Vista Clinical Research
state: South Carolina
city: Simpsonville
country: United States
facility: Hillcrest Clinical Research, LLC
state: South Carolina
city: Fayetteville
country: United States
facility: Middle Tennessee Clinical Research
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Memphis
country: United States
facility: Baptist Memorial Medical Group (Neurology Specialist - Headache Clinic)
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology, P.A.
state: Texas
city: Dallas
country: United States
facility: Radiant Research, Inc
state: Texas
city: Humble
country: United States
facility: Research Trials Worldwide, LLC
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC
state: Virginia
city: McLean
country: United States
facility: iNeuro Headache Specialist
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Research Center, LLC
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Neurology Specialists
state: Virginia
city: Seattle
country: United States
facility: Summit Research Network Seattle, LLC
state: Washington
city: Tacoma
country: United States
facility: South Puget Sound Neurology
state: Washington
city: Morgantown
country: United States
facility: West Virginia University, Department of Neurology
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Department of Neurology
state: Wisconsin
Study officials:
affiliation: Allergan
name: Adele Thorpe
role: STUDY_DIRECTOR
References:
citation: Johnston KM, Powell L, Popoff E, Harris L, Croop R, Coric V, L'Italien G. Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm. Clin J Pain. 2022 Nov 1;38(11):680-685. doi: 10.1097/AJP.0000000000001072.
citation: Lipton RB, Singh RBH, Revicki DA, Zhao S, Shewale AR, Lateiner JE, Dodick DW. Functionality, satisfaction, and global impression of change with ubrogepant for the acute treatment of migraine in triptan insufficient responders: a post hoc analysis of the ACHIEVE I and ACHIEVE II randomized trials. J Headache Pain. 2022 Apr 25;23(1):50. doi: 10.1186/s10194-022-01419-7.
citation: Blumenfeld AM, Knievel K, Manack Adams A, Severt L, Butler M, Lai H, Dodick DW. Ubrogepant Is Safe and Efficacious in Participants Taking Concomitant Preventive Medication for Migraine: A Pooled Analysis of Phase 3 Trials. Adv Ther. 2022 Jan;39(1):692-705. doi: 10.1007/s12325-021-01923-3. Epub 2021 Dec 7.
citation: Hutchinson S, Silberstein SD, Blumenfeld AM, Lipton RB, Lu K, Yu SY, Severt L. Safety and efficacy of ubrogepant in participants with major cardiovascular risk factors in two single-attack phase 3 randomized trials: ACHIEVE I and II. Cephalalgia. 2021 Aug;41(9):979-990. doi: 10.1177/03331024211000311. Epub 2021 Apr 19.
citation: Hutchinson S, Dodick DW, Treppendahl C, Bennett NL, Yu SY, Guo H, Trugman JM. Ubrogepant for the Acute Treatment of Migraine: Pooled Efficacy, Safety, and Tolerability From the ACHIEVE I and ACHIEVE II Phase 3 Randomized Trials. Neurol Ther. 2021 Jun;10(1):235-249. doi: 10.1007/s40120-021-00234-7. Epub 2021 Feb 20.
citation: Goadsby PJ, Blumenfeld AM, Lipton RB, Dodick DW, Kalidas K, M Adams A, Jakate A, Liu C, Szegedi A, Trugman JM. Time course of efficacy of ubrogepant for the acute treatment of migraine: Clinical implications. Cephalalgia. 2021 Apr;41(5):546-560. doi: 10.1177/0333102420970523. Epub 2020 Nov 26.
citation: Lipton RB, Dodick DW, Ailani J, Lu K, Finnegan M, Szegedi A, Trugman JM. Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. JAMA. 2019 Nov 19;322(19):1887-1898. doi: 10.1001/jama.2019.16711.