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.