TREXIMET® Versus Butalbital-containing Combination Medications for the Acute Treatment of Migraine in Adults
Condition: Migraine Disorders; Migraine, Acute
MeSH terms: Migraine Disorders
Intervention: TREXIMET®; Butalbital-containing Combination Medications (BCM); placebo
Intervention description: Sumatriptan + Naproxen Sodium (fixed dose combination tablet of sumatriptan succinate [equivalent to sumatriptan 85mg] and naproxen sodium 500mg); butalbital-containing combination medication (BCM; acetaminophen 325mg, caffeine 40mg, and butalbital 50mg) [currently marketed as Fioricet]; placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 375.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Migraine, acute; Migraine; Butalbital-containing Combination Medication (BCM); Naproxen sodium; Sumatriptan succinate; TREXIMET®

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)
    

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.