Efficacy, Safety, and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine (ACHIEVE II)

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine, With or Without Aura
• Intervention / Treatment: Drug: Ubrogepant; Drug: Placebo-matching Ubrogepant

• Study Type: Interventional
• Enrollment (Actual): 1686
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Clinical Research Advantage, Inc./Simon Williamson Clinic
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Clinical Research Advantage, Inc./East Valley Family Physicians, PLC
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital & Medical Center - Barrow Neurologic Institute (BNI)
    • Phoenix, Arizona, United States, 85020
      • Clinical Research Advantage, Inc./Central Phoenix Medical Clinic, LLC
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona, May Clinic Scottsdale
    • Tucson, Arizona, United States, 85712
      • Radiant Research Inc.
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Apple Valley, California, United States, 92307
      • Axiom Research, LLC
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Colton, California, United States, 92324
      • Axiom Research, LLC
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center
    • Fresno, California, United States, 93720
      • California Headache and Balance Center
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • La Mesa, California, United States, 91942
      • Grossmont Center for Clinical Research
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Los Angeles, California, United States, 90024
      • California Advanced Neurotherapeutic, Inc.
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Pain Center
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Rancho Cucamonga, California, United States, 91730
      • Rancho Cucamonga Clinical Research
    • Rancho Mirage, California, United States, 92270
      • Desert Valley Research
    • Redondo Beach, California, United States, 90277
      • George J Rederich MD, Inc
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Vista, California, United States, 92083
      • Clinical Research Advantage, Inc./Cassidy Medical Group-Vista
  • Colorado
    • Colorado Springs, Colorado, United States, 80904
      • Clinicos, LLC
    • Englewood, Colorado, United States, 80113
      • Colorado Neurological Institute
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20016
      • Radiant Clinical Research
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura Neurological Associates
    • Coral Gables, Florida, United States, 33134
      • Clinical Research South Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Hollywood, Florida, United States, 33024
      • Broward Research Group
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Maitland, Florida, United States, 32751
      • Neurology Associates, P.A.
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute, LLC
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research, Corp.
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare, LLC
    • South Miami, Florida, United States, 33143
      • QPS MRA, LLC (Miami Research Associates)
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • The Kaufmann Clinic, Inc.
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc.
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Chicago, Illinois, United States, 60604
      • Clinical Research Advantage, Inc./Michigan Avenue Internists
    • Riverwoods, Illinois, United States, 60015
      • Robbins Headache Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology P.C.
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
    • Louisville, Kentucky, United States, 40207
      • Norton Neurology Services MS Services
  • Maryland
    • Baltimore, Maryland, United States, 21228
      • Seton Medical Group
    • Baltimore, Maryland, United States, 21236
      • Overlea Personal Physicians
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • BTC of New Bedford
    • Quincy, Massachusetts, United States, 02169
      • Beacon Clinical Research, LLC
    • Worcester, Massachusetts, United States, 01605
      • New England Regional Headache Center, Inc.
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • The Headache Center
  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Clinical Research Advantage, Inc./Prairie Fields Family Medicine, PC
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research, LLC
    • Omaha, Nebraska, United States, 68114
      • Clinical Research Advantage, Inc
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • HOPE Research Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
    • Skillman, New Jersey, United States, 08558
      • Princeton Center for Clinical Research
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • Great Neck, New York, United States, 11021
      • Cushing Neuroscience Institute North Shore-LIJ Medical Group
    • Plainview, New York, United States, 11803
      • ProHEALTH Care Associates, LLP
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates, LLC
    • Yonkers, New York, United States, 10701
      • Westchester Neuro. Const
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Carolina Headache Institute
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center, PC
    • Mooresville, North Carolina, United States, 28117
      • Lake Shore Clinical Research, LLC
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates, PA
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Plains Clinical Research Center, LLC
  • Ohio
    • Akron, Ohio, United States, 44311
      • Radiant Research, Inc.
    • Cincinnati, Ohio, United States, 45227
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45215
      • Patient Priority Clinical Sites, LLC
    • Cincinnati, Ohio, United States, 45212
      • Sentral Clinical Research Services
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Dept of Psychiatry & Behavioral Neuroscience
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Sooner Clinical Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Inc.
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates, Ltd.
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Radiant Research, Inc.
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
    • Columbia, South Carolina, United States, 29201
      • Vista Clinical Research
    • Simpsonville, South Carolina, United States, 29681
      • Hillcrest Clinical Research, LLC
  • Tennessee
    • Fayetteville, Tennessee, United States, 37334
      • Middle Tennessee Clinical Research
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Medical Group (Neurology Specialist - Headache Clinic)
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology, P.A.
    • Dallas, Texas, United States, 75234
      • Radiant Research, Inc
    • Humble, Texas, United States, 77338
      • Research Trials Worldwide, LLC
  • Utah
    • Ogden, Utah, United States, 84403
      • Advanced Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LLC
    • McLean, Virginia, United States, 22102
      • iNeuro Headache Specialist
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater
    • Roanoke, Virginia, United States, 24018
      • Blue Ridge Research Center, LLC
    • Virginia Beach, Virginia, United States, 23456
      • Sentara Neurology Specialists
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network Seattle, LLC
    • Tacoma, Washington, United States, 98409
      • South Puget Sound Neurology
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University, Department of Neurology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ubrogepant 25 mg; 1 ubrogepant 25 milligram (mg) tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, placebo-matching ubrogepant tablet or rescue medication, orally, 2 to 48 hours after initial dose.	Drug: Ubrogepant; Ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.; Drug: Placebo-matching Ubrogepant; Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.
Experimental: Ubrogepant 50 mg; 1 ubrogepant 50 mg tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, placebo-matching ubrogepant tablet or rescue medication, orally, 2 to 48 hours after initial dose.	Drug: Ubrogepant; Ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.; Drug: Placebo-matching Ubrogepant; Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.
Placebo Comparator: Placebo; 1 placebo-matching ubrogepant tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take placebo-matching ubrogepant tablet or rescue medication, orally, 2 to 48 hours after initial dose.	Drug: Placebo-matching Ubrogepant; Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Freedom at 2 Hours After Initial Dose	Pain freedom was defined as a reduction in headache pain severity from moderate/severe at baseline to no pain at 2 hours after the initial dose of investigational product. Participants were provided with electronic diary (eDiary) to rate headache severity on a scale from no pain to severe pain. Number analyzed is the number of participants with non-missing postdose pain severity assessment at or before 2 hours after initial dose.	Baseline (Predose) to 2 hours after initial dose
Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose	The most bothersome migraine-associated symptom was the symptom (photophobia, phonophobia or nausea) present at pre-dose baseline identified by the participant to be 'most bothersome'. Participants were provided with an eDiary to record absence or presence of migraine-associated symptoms. Number analyzed is the number of participants with non-missing postdose most bothersome migraine-associated symptoms assessed.	Baseline (Predose) to 2 hours after initial dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Relief at 2 Hours After the Initial Dose	Pain relief was defined as a reduction of a moderate/severe migraine headache to a mild headache or to no headache. Participants were provided with an eDiary to rate headache severity on a scale from no pain to severe pain. Number analyzed is the number of participants with non-missing pain severity assessment at or before 2 hours after initial dose.	Baseline (Predose) to 2 hours after initial dose
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours After Initial Dose	Sustained pain relief was defined as a pain relief at 2 hours with no administration of either rescue medication or the second dose of study drug, and with no occurrence thereafter of a moderate/severe headache up to 24 hours after dosing with study drug. Participants were provided with an eDiary to rate headache severity on a scale from no pain to severe pain. Determinable cases: participants for whom sustained pain relief from 2 to 24 hours status can be determined based on the observed headache severity at scheduled time points, use of rescue medication or optional second dose between 2 and 24 hours, and the answer to the headache recurrence question at 24 hours. Number analyzed is the number of participants with assessment of determinable sustained pain relief from 2 to 24 hours after initial dose.	2 to 24 hours after initial dose
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose	Sustained pain freedom was defined as a pain freedom at 2 hours with no administration of either rescue medication or the second dose of study drug, and with no occurrence thereafter of a mild/moderate/severe headache up to 24 hours after dosing with study drug. Participants were provided with an eDiary to rate headache severity on a scale from no pain to severe pain. Determinable cases: participants for whom sustained pain relief from 2 to 24 hours status can be determined based on the observed headache severity at scheduled time points, use of rescue medication or optional second dose between 2 and 24 hours, and the answer to the headache recurrence question at 24 hours. Number analyzed is the number of participants with assessment of determinable sustained pain freedom from 2 to 24 hours after initial dose.	2 to 24 hours after initial dose
Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose	Photophobia was defined as sensitivity to light, a migraine-associated symptom. Participants were provided with an eDiary to record absence or presence photophobia. Number analyzed is the number of participants with non-missing postdose photophobia assessment at or before 2 hours after initial dose.	2 hours after initial dose
Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose	Phonophobia was defined as sensitivity to sound, a migraine-associated symptom. Participants were provided with an eDiary to record absence or presence of phonophobia. Number analyzed is the number of participants with non-missing postdose phonophobia assessment at or before 2 hours after initial dose.	2 hours after initial dose
Percentage of Participants With Absence of Nausea at 2 Hours After the Initial Dose	Nausea was a migraine-associated symptom. Participants were provided with an eDiary to record absence or presence of nausea. Number analyzed is the number of participants with non-missing postdose nausea assessment at or before 2 hours after initial dose.	2 hours after initial dose

Collaborators and Investigators

• Sponsor: Allergan
• Investigators: Study Director: Adele Thorpe, Allergan

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. Erratum In: JAMA. 2020 Apr 7;323(13):1318.

Helpful Links

• More Information

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2016
• Primary Completion (Actual): January 25, 2018
• Study Completion (Actual): February 26, 2018

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (Estimate): August 16, 2016

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: UBR-MD-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No