TREXIMET� Versus Butalbital-containing Combination Medications for the Acute Treatment of Migraine in Adults

Condition(s) targeted: Migraine Disorders; Migraine, Acute

Intervention: TREXIMET® (Drug); Butalbital-containing Combination Medications (BCM) (Drug); placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

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)

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Number of Participants With a Sustained Pain-free (SPF) Response From 2 to 24 Hours Post-dose

Secondary outcome:

Number of Participants With a Pain-free Response From 2 to 48 Hours Post-dose

Number of Participants Using Rescue Medication Within 48 Hours Post Dose

Mean Time to First Use of Rescue Medication for the First Attack Treated With Study Medication (Attack 1)

Mean Time to First Use of Rescue Medication for the Second Attack Treated With Study Medication (Attack 2)

Mean Time to First Use of Rescue Medication for the Third Attack Treated With Study Medication (Attack 3)

Number of Participants With a Migraine-free Response 2-48 Hours After Dosing

Number of Participants With Pain-freedom and Relief of Nausea at 2, 4, 6, 8, 24 and 48 Post-dose Time Points

Number of Participants With Pain-freedom and Relief of Photophobia at 2, 4, 6, 8, 24 and 48 Post-dose Time Points

Number of Participants With Pain-freedom and Relief of Phonophobia at 2, 4, 6, 8, 24 and 48 Post-dose Time Points

Number of Participants With Pain-freedom and Relief of Vomiting at 2, 4, 6, 8, 24 and 48 Hours Post-dose

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

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

Number of Participants With Pain Relief at 2, 4, 6, 8, 24 and 48 Hours After Dosing Moderate or Severe Baseline Pain

Number of Participants Who Reported a Complete Symptom-Free Response at 2, 4, 6, 8, 24 and 48 Hours After Dosing

Mean Performance Index (PI) Scores at Time of Dosing and at 2, 4, 6, 8, 24 and 48 Hours After Dosing

Mean Stanford Sleepiness (SS) Scale Scores at Time of Dosing and at 2, 4, 6, 8, 24 and 48 Hours After Dosing

Efficacy Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Treating a Migraine

Functionality Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication

Ease-of-Use Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication

Bothersomeness-of-side Effect Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication

Total PPMQ-R Score as Measured With the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication

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)

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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 - 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.

GSK Investigational Site, Chandler, Arizona 85224, United States

GSK Investigational Site, Gilbert, Arizona 85234, United States

GSK Investigational Site, Litchfield Park, Arizona 85340, United States

GSK Investigational Site, Mesa, Arizona 85213, United States

GSK Investigational Site, Phoenix, Arizona 85014, United States

GSK Investigational Site, Tempe, Arizona 85283, United States

GSK Investigational Site, Little Rock, Arkansas 72201, United States

GSK Investigational Site, Little Rock, Arkansas 72205, United States

GSK Investigational Site, Anaheim, California 92801, United States

GSk Investigational Site, Anaheim, California 92805, United States

GSK Investigational Site, Garden Grove, California 92845, United States

GSK Investigational Site, Irvine, California 92618, United States

GSK Investigational Site, Newport Beach, California 92660, United States

GSK Investigational Site, Northridge, California 91325, United States

GSK Investigational Site, Riverside, California 92501, United States

GSK Investigational Site, Sacramento, California 92585, United States

GSK Investigational Site, San Diego, California 92108, United States

GSK Investigational Site, San Francisco, California 94109, United States

GSK Investigational Site, Santa Monica, California 90404, United States

GSK Investigational Site, Sherman Oaks, California 91403, United States

GSK Investigational Site, Walnut Creek, California 94596, United States

GSK Investigational Site, Westlake Village, California 91361, United States

GSK Investigational Site, Colorado Springs, Colorado 80909, United States

GSK Investigational Site, East Hartford, Connecticut 06118, United States

GSK Investigational Site, New Britain, Connecticut 06050, United States

GSK Investigational Site, Clearwater, Florida 33755, United States

GSK Investigational Site, Daytona Beach, Florida 32117, United States

GSK Investigational Site, Deland, Florida 32720, United States

GSK Investigational Site, Naples, Florida 34102, United States

GSK Investigational Site, Pembroke Pines, Florida 33024, United States

GSK Investigational Site, Plantation, Florida 33324, United States

GSK Investigational Site, West Palm Beach, Florida 33407-2450, United States

GSK Investigational Site, Atlanta, Georgia 30309, United States

GSK Investigational Site, Atlanta, Georgia 30342, United States

GSK Investigational Site, Rome, Georgia 30165, United States

GSK Investigational Site, Savannah, Georgia 31406, United States

GSK Investigational Site, Suwanee, Georgia 30024, United States

GSK Investigational Site, Chicago, Illinois 60614, United States

GSK Investigational Site, Gurnee, Illinois 60031, United States

GSK Investigational Site, Maywood, Illinois 60153, United States

GSK Investigational Site, Indianapolis, Indiana 46256, United States

GSK Investigational Site, Paducah, Kentucky 42003, United States

GSK Investigational Site, Shreveport, Louisiana 71101, United States

GSK Investigational Site, Shreveport, Louisiana 71103, United States

GSK Investigational Site, Biddeford, Maine 04005, United States

GSK Investigational Site, Pikesville, Maryland 21208, United States

GSk Investigational Site, Brockton, Massachusetts 02301, United States

GSK Investigational Site, Springfield, Massachusetts 01104, United States

GSK Investigational Site, Ann Arbor, Michigan 48104, United States

GSK Investigational Site, Kalamazoo, Michigan 49009, United States

GSK Investigational Site, Hattiesburg, Mississippi 39401, United States

GSK Investigational Site, Springfield, Missouri 65807, United States

GSK Investigational Site, St. Louis, Missouri 63141, United States

GSK Investigational Site, Henderson, Nevada 89014, United States

GSK Investigational Site, Las Vegas, Nevada 89119, United States

GSK Investigational Site, Cherry Hill, New Jersey 08002, United States

GSK Investigational Site, Ridgewood, New Jersey 07550, United States

GSK Investigational Site, Stratford, New Jersey 08084, United States

GSK Investigational Site, Albuquerque, New Mexico 87108, United States

GSK Investigational Site, Albany, New York 12205, United States

GSK Investigational Site, Albany, New York 12206, United States

GSK Investigational Site, Bronx, New York 10461, United States

GSK Investigational Site, Brooklyn, New York 11235, United States

GSK Investigational Site, Mount Vernon, New York 10550, United States

GSK Investigational Site, New York, New York 10022, United States

GSK Investigational Site, New York, New York 10021, United States

GSK Investigational Site, Orchard Park, New York 14127, United States

GSK Investigational Site, Schenectady, New York 12308, United States

GSK Investigational Site, Syracuse, New York 13210, United States

GSK Investigational Site, Valley Stream, New York 11580, United States

GSK Investigational Site, Cary, North Carolina 27518, United States

GSK Investigational Site, Charlotte, North Carolina 28204, United States

GSK Investigational Site, Greenville, North Carolina 27858, United States

GSK Investigational Site, Hickory, North Carolina 28601, United States

GSK Investigational Site, Wilmington, North Carolina 28401, United States

GSK Investigational Site, Winston-Salem, North Carolina 27103, United States

GSK Investigational Site, Bismarck, North Dakota 58501, United States

GSK Investigational Site, Fargo, North Dakota 58104, United States

GSK Investigational Site, Minot, North Dakota 58704, United States

GSK Investigational Site, Cincinnati, Ohio 45245, United States

GSK Investigational Site, Cincinnati, Ohio 45227, United States

GSK Investigational Site, Cleveland, Ohio 44122, United States

GSK Investigational Site, Columbus, Ohio 43210, United States

GSK Investigational Site, Dayton, Ohio 45406, United States

GSK Investigational Site, Toledo, Ohio 43614-5809, United States

GSK Investigational Site, Oklahoma City, Oklahoma 73112, United States

GSK Investigational Site, Greensburg, Pennsylvania 15601, United States

GSK Investigational Site, Philadelphia, Pennsylvania 19107, United States

GSK Investigational Site, Philadelphia, Pennsylvania 19114, United States

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GSK Investigational Site, Warwick, Rhode Island 02886, United States

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GSK Investigational Site, Columbia, Tennessee 38401, United States

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GSK Investigational Site, Austin, Texas 78745, United States

GSK Investigational Site, Dallas, Texas 75231, United States

GSK Investigational Site, Dallas, Texas 75234, United States

GSK Investigational Site, Houston, Texas 77004, United States

GSK Investigational Site, San Antonio, Texas 78229, United States

GSK Investigational Site, San Antonio, Texas 78258, United States

GSK Investigational Site, Salt Lake City, Utah 84107, United States

GSK Investigational Site, Virginia Beach, Virginia 23452, United States

Related publications:

Silberstein SD, McCrory DC. Butalbital in the treatment of headache: history, pharmacology, and efficacy. Headache. 2001 Nov-Dec;41(10):953-67. Review.

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.

Wenzel RG, Sarvis CA. Do butalbital-containing products have a role in the management of migraine? Pharmacotherapy. 2002 Aug;22(8):1029-35. Review.

Starting date: February 2008
Last updated: November 30, 2010