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Sumatriptan-Naproxen and Butalbital: A Double-Blind, Placebo-Controlled Crossover Study

Authors

  • Frederick Derosier DO,

    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Fred Sheftell MD,

    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Stephen Silberstein MD,

    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Roger Cady MD,

    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Gary Ruoff MD,

    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Alok Krishen MS,

    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Margaret Peykamian BSPH

    Corresponding author
    1. From GlaxoSmithKline—Neurosciences, Research Triangle Park, NC, USA (M. Peykamian, F. Derosier, and A. Krishen); New England Center for Headache, Stamford, CT, USA (F. Sheftell); Thomas Jefferson University—Neurology, Philadelphia, PA, USA (S. Silberstein); Banyan Group Inc.—Headache, Springfield, MO, USA (R. Cady); Westside Family Medical Center—Family Practice, Kalamazoo, MI, USA (G. Ruoff).
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  • Conflict of Interest: Frederick J. Derosier, Alok Krishen, and Margaret A. Peykamian are employees of GlaxoSmithKline. Roger Cady is consultant for GlaxoSmithKline, Merck, Ortho-McNeil. He received research grants from Allergan, Endo Pharmaceuticals, GlaxoSmithKline, Merck, Pozen, PuraMed Bioscience, and Wyeth. Fred D. Sheftell, is with the speaker's bureau of Merck, GSK, Nautilus, Zogenix. He is also a member of the advisory board of Merck, GSK, Nautilus, Allergan, NuPathe, MAP, and Pfizer. Stephen D. Silberstein is on the advisory panel of and receives honoraria from AGA, Allergan, Amgen, Capnia, Coherex, GlaxoSmithKline, Lilly, MAP, Medtronic, Merck, Minster, Neuralieve, NINDS, NuPathe, Pfizer, St. Jude Medical, and Valeant Pharmaceuticals. He is on the speakers' bureau of and receives honoraria from Endo Pharmaceuticals, GlaxoSmithKline, and Merck. He serves as a consultant for and receives honoraria from Amgen, Novartis, and Opti-Nose. His employer receives research support from AGA, Allergan, Boston Scientific, Capnia, Coherex, Endo Pharmaceuticals, GlaxoSmithKline, Lilly, MAP, Medtronic, Merck, NINDS, NuPathe, St. Jude Medical, and Valeant Pharmaceuticals. Gary Ruoff is a GSK investigator, and a member of the GSK advisory board and speaker's bureau.

  • Clinical Trials Registration: NCT00573170.

M. Peykamian, GlaxoSmithKline—Neurosciences, 5 Moore Drive, Research Triangle Park, NC 27709, USA, email: ma4104@gsk.com

Abstract

Objectives.— The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap—85 mg sumatriptan and 500 mg naproxen sodium), a butalbital-containing combination medication (BCM—50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past.

Background.— Despite the lack of Food and Drug Administration approval and the absence of placebo-controlled trials to demonstrate efficacy, butalbital-containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital-containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication-overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo.

Methods.— Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2-24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double-blind, double-dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition).

Results.— A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test-6 of >59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28-29% of subjects took study medication within 15 minutes of migraine onset, 34-37% of subjects took study medication >15 minutes to 2 hours after onset, and 32-36% of subjects took study medication more than 2 hours after onset.

This study did not detect a difference at the nominal 0.05 level in percent sustained pain-free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P ≤ .044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P ≤ .01); sustained pain relief 2-24 hours (P < .001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P ≤ .046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P ≤ .031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and <1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication.

Conclusions.— This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital-containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.

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