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CompletedNCT02191579Updated Jun 7, 2018Results posted

Efficacy and Safety Study of BOTOX® Compared to Topiramate for the Prevention of Chronic Migraine in Adults

A Phase 4 interventional study of onabotulinumtoxinA and Topiramate in Migraine Disorders, sponsored by Allergan. Completed at 32 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-06-07.

Sponsored by Allergan (part of AbbVie) · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
282
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This study will evaluate the efficacy, safety and tolerability of prophylactic (preventative) treatment with BOTOX® (onabotulinumtoxinA) compared to topiramate in adults with chronic migraine.

02

Conditions studied

  • Migraine Disorders

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03

In context

Migraine Disorders

1,558 studies on the registry are indexed under Migraine Disorders; 301 are open to participants now.

This study's enrollment of 282 is above the median of 80 across 1,197 interventional studies indexed under Migraine Disorders.

Browse Migraine Disorders studies →

Lead sponsor

Allergan is the lead sponsor of 505 studies on the registry; none are open to participants now.

Of its 93 completed or terminated interventional studies of FDA-regulated products, 91 (98%) have results posted.

First submitted before Allergan became part of AbbVie.

Browse Allergan studies →All AbbVie studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • History of chronic migraine
  • More than 15 headache days in a 28 day period (headaches that last more than 4 hours and/or require treatment with prescription medication).

Exclusion criteria

Exclusion Criteria:

  • Taking opioid-containing products for acute headache treatment more than 8 days during a 28-day period
  • Previous treatment with botulinum toxin of any serotype for any reason
  • Previous treatment with topiramate
  • On a ketogenic diet (high in fat, low in carbohydrates)
  • History of acute myopia or increased intraocular pressure
  • Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis or any other significant disease that might interfere with neuromuscular function
  • Acupuncture, transcutaneous electrical stimulation (TENS), cranial traction, dental splints for headache, or injection of anesthetics/steroids in the 4 weeks prior to screening.
05

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
282 participants (actual)

Study arms

  • Active comparator
    BOTOX®

    155U onabotulinumtoxinA (BOTOX®) total dose per treatment by intramuscular injection every 12 weeks for up to 3 treatments.

    Biological: onabotulinumtoxinA

  • Active comparator
    Topiramate

    Topiramate starting at a daily oral dose of 25 mg/day titrated up to a maximum dose of 100 mg/day for 36 weeks. Participants who discontinue topiramate are eligible to receive treatment with BOTOX®.

    Drug: Topiramate

Interventions

  • BiologicalonabotulinumtoxinA

    155U onabotulinumtoxinA (BOTOX®) total dose per treatment by intramuscular injection every 12 weeks.

    Also known as: BOTOX®, botulinum toxin Type A

  • DrugTopiramate

    Topiramate up to a maximum oral dose of 100 mg/day.

    Also known as: Topamax®

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days

    Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 50% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported.

    Time frame: Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32

Secondary outcomes

  1. Change From Baseline in the Frequency of Headache Days Per 28-day Period

    Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. A negative change from Baseline (less headache days) indicates improvement.

    Time frame: Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32

  2. Change From Baseline in Headache Impact Test (HIT-6) Total Score

    The HIT-6 is a valid disease-targeted measure used to assess the impact of headaches, comprised of 6 items that assess pain, role functioning, social functioning, cognitive functioning, vitality, and psychological distress. A total score is created by summingacross all items, and ranges from 36 (no impact) to 78 (severe impact) reflecting a "best to worst" scoring. A negative change from Baseline (a lower score) indicates improvement.

    Time frame: Baseline (Day 1) to the last 28-day period ending with Week 30

  3. Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days

    Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 70% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported.

    Time frame: Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32

07

Results

Posted Jun 7, 2018

Participant flow

Treatment 1
Participant flow — Treatment 1
MilestoneBOTOX®Topiramate/BOTOX®
Started140142
Completed11384
Not completed2758
Withdrew: Multiple reasons specified2758
Treatment 2
Participant flow — Treatment 2
MilestoneBOTOX®Topiramate/BOTOX®
Started080
Completed055
Not completed025
Withdrew: Multiple reasons specified025

Outcome measures

PrimaryPercentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days

Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 50% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported.

Time frame:
Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32
Reported as:
Number · percentage of participants
Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days
percentage of participantsBOTOX®Topiramate
Percentage of Participants With a ≥ 50% Decrease From Baseline in the Frequency of Headache Days40.012.0
Statistical analysis
  • BOTOX® vs Topiramate · Regression, Logistic · p = <0.001 (Odds ratio, 95% CI, and p-value were estimated using a logistic regression model adjusted by baseline headache days.) · Odds ratio (or): 4.94 · 95% CI 2.681 to 9.085
SecondaryChange From Baseline in the Frequency of Headache Days Per 28-day Period

Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. A negative change from Baseline (less headache days) indicates improvement.

Time frame:
Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32
Reported as:
Mean · days
Change From Baseline in the Frequency of Headache Days Per 28-day Period
daysBOTOX®Topiramate
Change From Baseline in the Frequency of Headache Days Per 28-day Period-8.3 ± 8.9-2.1 ± 5.6
Statistical analysis
  • BOTOX® vs Topiramate · ANCOVA · p = <0.001 (Estimated mean difference, 95% CI, and p-value were assessed using analysis of covariance adjusting for baseline headache days.) · Mean difference (net): -6.199 · 95% CI -7.936 to -4.462
SecondaryChange From Baseline in Headache Impact Test (HIT-6) Total Score

The HIT-6 is a valid disease-targeted measure used to assess the impact of headaches, comprised of 6 items that assess pain, role functioning, social functioning, cognitive functioning, vitality, and psychological distress. A total score is created by summingacross all items, and ranges from 36 (no impact) to 78 (severe impact) reflecting a "best to worst" scoring. A negative change from Baseline (a lower score) indicates improvement.

Time frame:
Baseline (Day 1) to the last 28-day period ending with Week 30
Reported as:
Mean · score on a scale
Change From Baseline in Headache Impact Test (HIT-6) Total Score
score on a scaleBOTOX®Topiramate
Change From Baseline in Headache Impact Test (HIT-6) Total Score-5.6 ± 7.2-1.3 ± 3.9
Statistical analysis
  • BOTOX® vs Topiramate · ANCOVA · p = <0.001 (Estimated mean difference, 95% CI, and p-value for Week 30 were assessed using analysis of covariance adjusting for baseline headache days.) · Median difference (net): -4.248 · 95% CI -5.766 to -2.731
SecondaryPercentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days

Participants recorded their headaches in a daily e-diary. A headache day was defined as a calendar day (00:00 to 23:59) with 4 or more hours of headache and/or headache of any duration with the use of migraine-specific acute headache medication(s). The number of headache days over the 28-day period was counted. The percentage of participants with a ≥ 70% decrease in headache days in the 28-day period prior to Week 32 relative to Baseline (28-day period prior to Day 1) is reported.

Time frame:
Baseline (First 28 days from Screening) to the last 28-day period ending with Week 32
Reported as:
Number · percentage of participants
Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days
percentage of participantsBOTOX®Topiramate
Percentage of Participants With a ≥ 70% Decrease From Baseline in the Frequency of Headache Days27.18.5
Statistical analysis
  • BOTOX® vs Topiramate · Regression, Logistic · p = <0.001 (Odds ratio, 95% CI, and p-value for the Week 29-32 interval were estimated using a logistic regression model adjusted by baseline headache days.) · Odds ratio (or): 4.05 · 95% CI 2.014 to 8.157

Adverse events

Collected over First dose of study drug to the final visit (Up to 48 Weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BOTOX®0/220 (0%)4/220 (1.8%)27/220 (12.3%)
Topiramate0/142 (0%)6/142 (4.2%)89/142 (62.7%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventBOTOX®Topiramate
ConcussionInjury, poisoning and procedural complications1/2201/142
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders1/2201/142
Deep vein thrombosisVascular disorders0/2201/142
DehydrationMetabolism and nutrition disorders0/2201/142
NephrolithiasisRenal and urinary disorders0/2201/142
Peripheral arterial occlusive diseaseVascular disorders0/2201/142
PneumoniaInfections and infestations1/2201/142
Road traffic accidentInjury, poisoning and procedural complications1/2201/142
Atrial tachycardiaCardiac disorders1/2200/142
Invasive lobular breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/2200/142
Most frequent other events
Most frequent other events
EventBOTOX®Topiramate
ParaesthesiaNervous system disorders1/22044/142
NauseaGastrointestinal disorders1/22019/142
FatigueGeneral disorders1/22019/142
DizzinessNervous system disorders6/22018/142
Cognitive DisorderNervous system disorders1/22018/142
Decreased appetiteMetabolism and nutrition disorders0/22015/142
Distubance in attentionNervous system disorders0/22012/142
Vision blurredEye disorders6/22011/142
SinusitisInfections and infestations13/22010/142
DepressionPsychiatric disorders4/2208/142

Baseline characteristics

Intent-to-treat (ITT) Set included all randomized participants.

Age, Continuous
Age, Continuous(years)BOTOX®TopiramateTotal
Mean40.2 ± 11.739.4 ± 12.639.8 ± 12.1
Age, Customized
Age, Customized(Participants)BOTOX®TopiramateTotal
18 to <25162137
25 to <35304070
35 to <45432972
45 to <55333467
≥55181836
Sex: Female, Male
Sex: Female, Male(Participants)BOTOX®TopiramateTotal
Female117122239
Male232043
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)BOTOX®TopiramateTotal
White111118229
Black13821
Asian426
Hispanic111223
Other123
Height
Height(centimeter (cm))BOTOX®TopiramateTotal
Mean167.4 ± 8.5167.0 ± 8.7167.2 ± 8.5
Weight
Weight(kilogram (kg))BOTOX®TopiramateTotal
Mean81.0 ± 21.880.5 ± 20.680.8 ± 21.1
Body Mass Index (BMI
Body Mass Index (BMI(kg/m^2)BOTOX®TopiramateTotal
Mean28.9 ± 7.128.8 ± 6.528.8 ± 6.8
Use of Headache Prophylactic Treatment(s)
Use of Headache Prophylactic Treatment(s)(Participants)BOTOX®TopiramateTotal
Count of participants262551
08

Study locations

32 sites
  • St Joseph's Hospital Barrow Neurology Clinics
    Phoenix, Arizona 85013, United States
  • North County Neurology Associates
    Encinitas, California 92024, United States
  • California Headache and Balance Center
    Fresno, California 93723, United States
  • Newport Beach Clinical Research Associates, Inc.
    Newport Beach, California 92663, United States
  • Denver Neurological Clinic
    Denver, Colorado 80210, United States
  • Ki Health Partners LLC DBA New England Institute for Neurology and Headache
    Stamford, Connecticut 06905, United States
  • Parkinson's Disease and Movement Disorders Center of Boca Raton Inc
    Boca Raton, Florida 33486, United States
  • Design Neuroscience Center
    Doral, Florida 33172, United States
  • NW FL Clinical Research Group, LLC
    Gulf Breeze, Florida 32561, United States
  • Negroski, Sutherland & Hanes Neurology
    Sarasota, Florida 34239, United States
  • Neurology Research Institute at Palm Beach Neurology
    West Palm Beach, Florida 33407, United States
  • Robbins Headache Clinic
    Riverwoods, Illinois 60015, United States
  • International Clinical Research Institute Inc
    Overland Park, Kansas 66210, United States
  • Kansas City Bone and Joint Clinic
    Overland Park, Kansas 66211, United States
  • The NeuroMedical Center
    Baton Rouge, Louisiana 70810, United States
  • MedVadis Research Corporation
    Watertown, Massachusetts 02472, United States
  • New England Regional Headache Center Inc
    Worcester, Massachusetts 01605, United States
  • Allegiance Health
    Jackson, Michigan 49201, United States
  • Clinvest
    Springfield, Missouri 65807, United States
  • Mercy Health Research
    St Louis, Missouri 63141, United States
  • Renown Institute for Neurosciences
    Reno, Nevada 89502, United States
  • Dent Neurosciences Research Center Incorporated
    Amherst, New York 14226, United States
  • Island Neurological Associates PC
    Plainview, New York 11803, United States
  • Montefiore Headache Center
    The Bronx, New York 10461, United States
  • Asheville Neurology Specialists PA
    Asheville, North Carolina 28806, United States
  • Headache Wellness Center
    Greensboro, North Carolina 27405, United States
  • Raleigh Neurology Associates PA
    Raleigh, North Carolina 27607, United States
  • Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
  • Preferred Primary Care Physicians
    Pittsburgh, Pennsylvania 15236, United States
  • Main Line Health Lankenau Hospital
    Wynnewood, Pennsylvania 19096, United States
  • Texas Neurology
    Dallas, Texas 75214, United States
  • Puget Sound Neurology
    Tacoma, Washington 98409, United States
09

References and documents

Publications

  • Blumenfeld AM, Patel AT, Turner IM, Mullin KB, Manack Adams A, Rothrock JF. Patient-Reported Outcomes from a 1-Year, Real-World, Head-to-Head Comparison of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine. J Prim Care Community Health. 2020 Jan-Dec;11:2150132720959936. doi: 10.1177/2150132720959936. PubMed 32985341 ↗
  • Rothrock JF, Adams AM, Lipton RB, Silberstein SD, Jo E, Zhao X, Blumenfeld AM; FORWARD Study investigative group. FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine. Headache. 2019 Nov;59(10):1700-1713. doi: 10.1111/head.13653. Epub 2019 Sep 26. PubMed 31559634 ↗

Study documents

  • Statistical analysis plan · Jul 17, 2017
  • Study protocol · May 27, 2014

Documents are hosted by the registry — open the source record to download them.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Aug 2014 to primary completion in May 2017, 33 months.

Results were first posted in Jun 2018, 1 year after primary completion.

Of 27 industry-sponsored phase 4 interventional studies under Migraine Disorders, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 33. This study's 33 months is above that.

Counting every sponsor, half of 77 studies reached it within 27 months; a quarter within 17 and three quarters within 37.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 14, 2014
First posted
Jul 16, 2014
StartActual
Aug 5, 2014
Primary completionActual
May 9, 2017
CompletionActual
Sep 1, 2017
Results first posted
Jun 7, 2018
Last update
Jun 7, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 7, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02191579
Lead sponsor
Allergan
Responsible party
Sponsor
First posted
Jul 16, 2014
Start date
Aug 5, 2014
Primary completion
May 9, 2017
Completion
Sep 1, 2017
Results posted
Jun 7, 2018
Last update
Jun 7, 2018

Study contacts

Esther Jo
study director · Allergan

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Botulinum toxin type A · Topiramate

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