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

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 (50 and 100 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: Placebo-matching Ubrogepant; Drug: Ubrogepant

• Study Type: Interventional
• Enrollment (Actual): 1672
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85213
      • Clinical Research Advantage, Inc./Desert Clinical Research, LLC.
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc.
    • Tucson, Arizona, United States, 85741
      • Clinical Research Advantage, Inc./Orange Grove Family Practice
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Principals Research Group, Inc.
    • Little Rock, Arkansas, United States, 72205
      • KLR Business Group, Inc. dba Arkansas Clinical Research
  • California
    • Carlsbad, California, United States, 92011
      • The Research Center of Southern California, LLC
    • Carmichael, California, United States, 95608
      • Med Center
    • Encino, California, United States, 91436
      • T. Joseph Raoof MD, Inc./Encino Research Center
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Laguna Hills, California, United States, 92656
      • Prime Care Clinical Research
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC.
    • National City, California, United States, 91950
      • Synergy San Diego
    • Newport Beach, California, United States, 92663
      • Newport Beach Clinical Research Associates, Inc.
    • Oceanside, California, United States, 92054
      • North County Clinical Research
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • Santa Monica, California, United States, 90404
      • CA Medical Clinic for Headache
    • Simi Valley, California, United States, 93065
      • Southern California Research LLC
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Alpine Clinical Research Center, Inc.
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves, INC
    • Denver, Colorado, United States, 80210
      • Denver Neurological Research
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Associated Neurologists, P.C.
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurolgists of Southern Connecticut, PC
  • Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hallandale Beach, Florida, United States, 33009
      • CPI MD Clinical
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research, LLC
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Palm Beach Gardens, Florida, United States, 33410
      • Palm Beach Neurological Center/Advanced Research Consultants, Inc.
    • Spring Hill, Florida, United States, 34609
      • Meridien Research
    • Tampa, Florida, United States, 33612
      • University of South Florida
    • Tampa, Florida, United States, 33634
      • Meridien Research
    • West Palm Beach, Florida, United States, 33407
      • Neurology Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Midtown Neurology
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic, Medical Office Building 1 Research Institute
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • Rowe Neurology Institute
    • Overland Park, Kansas, United States, 66211
      • Kansas Institute of Research
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Center Physicians Group - Neurology Research Department
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/Adult Research
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • South Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates, Inc
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research Corporation
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head-Pain & Neurological Institute
    • Kalamazoo, Michigan, United States, 49009
      • Beyer Research
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
  • Missouri
    • Springfield, Missouri, United States, 65810
      • Clinvest Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89117
      • Clinical Research Advantage, Inc./Diagnostic Center of Medicine - Durango
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience, Inc.
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Neurology Associates, P.A.
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC.
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clinical Research, Inc.
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc
    • Lyndhurst, Ohio, United States, 44124
      • Ohio Clinical Research, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73103
      • MPH IPS Research Company
    • Oklahoma City, Oklahoma, United States, 73109
      • NPC Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
    • Portland, Oregon, United States, 97214
      • Oregon Center For Clinical Investigations Inc. (OCCI, Inc.)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research Of Philadelphia, Llc
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • BTC of Lincoln
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc.
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research, LLC
    • San Antonio, Texas, United States, 78249
      • Road Runner Research, Ltd.
    • San Antonio, Texas, United States, 78229
      • Clinical Trials Texas, Inc
  • Utah
    • Draper, Utah, United States, 84020
      • J. Lewis Research, Inc. / Foothill Family Clinic Draper
    • Riverton, Utah, United States, 84065
      • Granger Medical Clinic-Riverton
    • Salt Lake City, Utah, United States, 84102
      • Optimum Clinical Research, Inc.
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98104
      • The Polyclinic Madison Center

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 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, diarrhea 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 50 mg; 1 ubrogepant 50 mg tablet and 1 placebo-matching ubrogepant 50 mg tablet, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, 2 placebo-matching ubrogepant tablets or rescue medication, orally 2 to 48 hours after initial treatment.	Drug: Placebo-matching Ubrogepant; Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.; Drug: Ubrogepant; 50 mg ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.
Experimental: Ubrogepant 100 mg; 2 Ubrogepant 50 mg tablets, orally for treatment of a qualifying migraine attack. Participants had the option to take a second dose, 2 placebo-matching ubrogepant tablets or rescue medication, orally 2 to 48 hours after initial treatment.	Drug: Placebo-matching Ubrogepant; Placebo-matching ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.; Drug: Ubrogepant; 50 mg ubrogepant tablet(s) orally for the treatment of a qualifying migraine attack.
Placebo Comparator: Placebo; 2 placebo-matching ubrogepant 50 mg tablets, orally for treatment of a qualifying migraine attack. Participants had the option to take 2-placebo-matching ubrogepant tablets or rescue medication, orally 2 to 48 hours after initial treatment.	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 severity from moderate/severe at baseline to no pain at 2 hours after the initial dose. Participants were provided with an 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.	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 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
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 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 determinable sustained pain freedom from 2 to 24 hours after initial dose.	2 to 24 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.
• Dodick DW, Lipton RB, Ailani J, Lu K, Finnegan M, Trugman JM, Szegedi A. Ubrogepant for the Treatment of Migraine. N Engl J Med. 2019 Dec 5;381(23):2230-2241. doi: 10.1056/NEJMoa1813049.

Helpful Links

• More Information

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2016
• Primary Completion (Actual): December 13, 2017
• Study Completion (Actual): December 14, 2017

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 7, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 13, 2018
• Last Verified: December 1, 2018

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-01

Drug and device information, study documents

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