Clinical trial NCT00573170: TREXIMET® Versus Butalbital-containing Combination Medications for the Acute Treatment of Migraine in Adults
Official title: A Randomized, Double-blind, Double-dummy, Placebo-controlled, Crossover Study to Evaluate the Efficacy of TREXIMET® (Sumatriptan + Naproxen Sodium) vs. Butalbital-containing Combination Medications for the Acute Treatment of Migraine When Administered During the Moderate-Severe Migraine Pain, Studies 1 and 2 of 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine Disorders
Migraine, Acute
Keywords: Migraine, acute
Migraine
Butalbital-containing Combination Medication (BCM)
Naproxen sodium
Sumatriptan succinate
TREXIMET®
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-12-14
Enrollment: 375
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Study TRX109011/TRX109013, A Randomized, Double-blind, Double-dummy, Placebo-controlled, Crossover Study to Evaluate the Efficacy of TREXIMET® (Sumatriptan + Naproxen Sodium) versus Butalbital-containing Combination Medications (BCM) for the Acute Treatment of Migraine when administered during the Moderate-Severe Pain Phase of the Migraine (Studies 1 and 2 of 2)

Detailed description: This study is a multicenter, randomized, double-blind, double-dummy, placebo-controlled, crossover, three-attack, outpatient study in which TREXIMET® will be compared to a butalbital-containing combination medication (BCM; acetaminophen 325mg, caffeine 40mg, and butalbital 50mg \[Fioricet\]) for the acute treatment of migraine headaches. Subjects will be randomized to one of 6 possible treatment sequences (TPB, TBP, BTP, BPT, PTB, PBT where T = TREXIMET®; P = Placebo; B = Butalbital-containing Combination Medication) . Subjects will treat each of the 3 migraine attacks when pain is moderate to severe. The study will include 4 visits: (1) a Screening visit at study entry, (2) a Drug Screen visit, (3) a Randomization visit, and (4) a Final visit. The Final visit occurs either (A) upon withdrawal or (B) after treatment of 3 migraine attacks. The primary objective is to evaluate the efficacy of TREXIMET® versus BCM for the acute treatment of moderate/severe migraine. These two replicate studies were amended while ongoing to allow for the reporting of pooled data only.

Eligibility criteria: Inclusion Criteria:

* Males and females aged 18 to 65 years. Female subjects are eligible for participation if they are either of non-childbearing potential (not capable of becoming pregnant) OR of childbearing potential having a negative urine pregnancy test at screening, and using contraception if sexually active. If using oral contraceptives, the subjects should be on a stable regimen of oral contraceptives (\>/= 2 months).

Eligible subjects must:

* have migraine with or without aura (2004 ICHD-II criteria) and must have had at least 2 attacks per month meeting these criteria in the three months prior to screening.
* have documented use of Butalbital-containing Combination Medication (MCM) to have treated at least one migraine.
* be able to understand how to complete the cognitive assessments and all other questionnaires programmed in an electronic diary.
* be willing and able to provide written informed consent.

Exclusion Criteria:

A subject is not eligible if they have:

* \>8 migraines or \>/= 15 headache days per month in total, or has retinal, basilar, or hemiplegic migraine, or secondary headaches.
* taken \>350mg/day of butalbital and/or other barbiturates on an equivalent dose basis, on average, over the 30 days prior to screening.
* is likely to have unrecognized cardiovascular or cerebrovascular disease (based on history or risk factors).
* blood pressure \>/= 140/90mmHg in 2 out of 3 BP measurements or is taking any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker.
* history of congenital heart disease, cardiac arrhythmias requiring medication, or a clinical significant electrocardiogram abnormality.
* evidence or history of any ischemic vascular disease including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome, or signs/symptoms consistent with these.
* evidence or history of central nervous system pathology including stroke and/or transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower the convulsive threshold; or has been treated with an antiepileptic drug for seizure control within 5 years prior to screening.
* a history of impaired hepatic or renal function that contraindicates participation in the study.
* hypersensitivity, allergy, intolerance, or contraindication to the use of any triptan, NSAID, aspirin, barbiturates, or acetaminophen (including all sumatriptan and naproxen preparations), has porphyria or has nasal polyps and asthma.
* is currently taking, or has taken in the previous three months, an ergot preparation for migraine prophylaxis; or is taking a migraine or prophylactic medication that is not stabilized (i.e. a change of dose within the last 2 months) for either chronic or intermittent migraine prophylaxis or for a co-morbid condition that is not stabilized.
* a recent history of regular use of opioids (including opioids in combination with butalbital, e.g. Fioricet with codeine) or barbiturates other than butalbital. Regular use is defined as an average of 4 days per month over the last 6 months.
* taken, or plans to take, a monoamine oxidase inhibitor (MAOI), including herbal preparations containing St. John's Wort (Hypericum perforatum), anytime within the 2 weeks prior to screening through 2 weeks post final study treatment.
* history of any bleeding disorder or is currently taking any anti-coagulant or any antiplatelet agent (except low-dose aspirin \</= 325mg/day for cardioprotective reasons).
* evidence or history of any gastrointestinal surgery or GI ulceration or perforation in the past six months, gastrointestinal bleeding in the past year; or evidence or history of inflammatory bowel disease.
* is pregnant, actively trying to become pregnant, breast feeding, or not willing to have pregnancy test performed.
* evidence of alcohol or substance abuse within the last year or any concurrent medical or psychiatric condition which, in the investigator's judgement, will likely interfere with the study conduct, subject cooperation, or evaluation and interpretation of the study results, or which otherwise contraindicates participation in this clinical study.
* participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during this study.

Primary outcomes:
measure: Number of Participants With a Sustained Pain-free (SPF) Response From 2 to 24 Hours Post-dose
timeFrame: From 2 to 24 hours post-dose. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
Secondary outcomes:
measure: Number of Participants With a Pain-free Response From 2 to 48 Hours Post-dose
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants Using Rescue Medication Within 48 Hours Post Dose
timeFrame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Mean Time to First Use of Rescue Medication for the First Attack Treated With Study Medication (Attack 1)
timeFrame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Mean Time to First Use of Rescue Medication for the Second Attack Treated With Study Medication (Attack 2)
timeFrame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Mean Time to First Use of Rescue Medication for the Third Attack Treated With Study Medication (Attack 3)
timeFrame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With a Migraine-free Response 2-48 Hours After Dosing
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Pain-freedom and Relief of Nausea at 2, 4, 6, 8, 24 and 48 Post-dose Time Points
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Pain-freedom and Relief of Photophobia at 2, 4, 6, 8, 24 and 48 Post-dose Time Points
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Pain-freedom and Relief of Phonophobia at 2, 4, 6, 8, 24 and 48 Post-dose Time Points
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Pain-freedom and Relief of Vomiting at 2, 4, 6, 8, 24 and 48 Hours Post-dose
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Relief From Sinus/Facial Pain at 2, 4, 6, 8, 24 and 48 Hours After Dosing in Those Who Also Had the Symptom at Dosing
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Relief From Neck Pain at 2, 4, 6, 8, 24 and 48 Hours After Dosing Who Also Had the Symptom at Baseline
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants With Pain Relief at 2, 4, 6, 8, 24 and 48 Hours After Dosing Moderate or Severe Baseline Pain
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Number of Participants Who Reported a Complete Symptom-Free Response at 2, 4, 6, 8, 24 and 48 Hours After Dosing
timeFrame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Mean Performance Index (PI) Scores at Time of Dosing and at 2, 4, 6, 8, 24 and 48 Hours After Dosing
timeFrame: At time of dosing, and at 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Mean Stanford Sleepiness (SS) Scale Scores at Time of Dosing and at 2, 4, 6, 8, 24 and 48 Hours After Dosing
timeFrame: Dose time, 2, 4, 6, 8, 24 and 48 hours post-dose. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Efficacy Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Treating a Migraine
timeFrame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Functionality Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication
timeFrame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Ease-of-Use Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication
timeFrame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Bothersomeness-of-side Effect Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication
timeFrame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Total PPMQ-R Score as Measured With the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication
timeFrame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
measure: Numbers of Participants Able to "Engage in Normal Activities Not Impaired" at Time of Dosing and 2, 4, 6, and 8 Hours After Dosing as Assessed by the CDQ (Clinical Disability Questionnaire)
timeFrame: At dosing and at 2, 4, 6 and 8 hours after dosing of each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed).
Other outcomes:
Locations:
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: Gilbert
country: United States
facility: GSK Investigational Site
state: Arizona
city: Litchfield Park
country: United States
facility: GSK Investigational Site
state: Arizona
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
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facility: GSK Investigational Site
state: Arizona
city: Tempe
country: United States
facility: GSK Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Anaheim
country: United States
facility: GSk Investigational Site
state: California
city: Garden Grove
country: United States
facility: GSK Investigational Site
state: California
city: Irvine
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Northridge
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facility: GSK Investigational Site
state: California
city: Riverside
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facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
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facility: GSK Investigational Site
state: California
city: San Francisco
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facility: GSK Investigational Site
state: California
city: Santa Monica
country: United States
facility: GSK Investigational Site
state: California
city: Sherman Oaks
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Westlake Village
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: East Hartford
country: United States
facility: GSK Investigational Site
state: Connecticut
city: New Britain
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: GSK Investigational Site
state: Florida
city: Daytona Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Deland
country: United States
facility: GSK Investigational Site
state: Florida
city: Naples
country: United States
facility: GSK Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: GSK Investigational Site
state: Florida
city: Plantation
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
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state: Georgia
city: Rome
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state: Georgia
city: Savannah
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state: Georgia
city: Suwanee
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state: Georgia
city: Chicago
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state: Illinois
city: Gurnee
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city: Maywood
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city: Indianapolis
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state: Indiana
city: Paducah
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city: Shreveport
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state: Louisiana
city: Shreveport
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city: Biddeford
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state: Maine
city: Pikesville
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state: Maryland
city: Brockton
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facility: GSk Investigational Site
state: Massachusetts
city: Springfield
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city: Ann Arbor
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state: Michigan
city: Kalamazoo
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state: Michigan
city: Hattiesburg
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facility: GSK Investigational Site
state: Mississippi
city: Springfield
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facility: GSK Investigational Site
state: Missouri
city: St. Louis
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facility: GSK Investigational Site
state: Missouri
city: Henderson
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facility: GSK Investigational Site
state: Nevada
city: Las Vegas
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facility: GSK Investigational Site
state: Nevada
city: Cherry Hill
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Ridgewood
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facility: GSK Investigational Site
state: New Jersey
city: Stratford
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facility: GSK Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Albany
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facility: GSK Investigational Site
state: New York
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Brooklyn
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facility: GSK Investigational Site
state: New York
city: Mount Vernon
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Orchard Park
country: United States
facility: GSK Investigational Site
state: New York
city: Schenectady
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Valley Stream
country: United States
facility: GSK Investigational Site
state: New York
city: Cary
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Bismarck
country: United States
facility: GSK Investigational Site
state: North Dakota
city: Fargo
country: United States
facility: GSK Investigational Site
state: North Dakota
city: Minot
country: United States
facility: GSK Investigational Site
state: North Dakota
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Toledo
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Greensburg
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Warwick
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Beaufort
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Rapid City
country: United States
facility: GSk Investigational Site
state: South Dakota
city: Columbia
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Cordova
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Germantown
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Virginia Beach
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Silberstein SD, McCrory DC. Butalbital in the treatment of headache: history, pharmacology, and efficacy. Headache. 2001 Nov-Dec;41(10):953-67. doi: 10.1046/j.1526-4610.2001.01189.x.
citation: Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB. Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes. Cephalalgia. 2004 Jun;24(6):483-90. doi: 10.1111/j.1468-2982.2004.00691.x.
citation: Wenzel RG, Sarvis CA. Do butalbital-containing products have a role in the management of migraine? Pharmacotherapy. 2002 Aug;22(8):1029-35. doi: 10.1592/phco.22.12.1029.33595.
citation: Derosier F, Sheftell F, Silberstein S, Cady R, Ruoff G, Krishen A, Peykamian M. Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study. Headache. 2012 Apr;52(4):530-43. doi: 10.1111/j.1526-4610.2011.02039.x. Epub 2011 Nov 21.