Randomized, double-blind, crossover study comparing DFN-11 injection (3 mg subcutaneous sumatriptan) with 6 mg subcutaneous sumatriptan for the treatment of rapidly-escalating attacks of episodic migraine

Abstract

Background: A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy.

Methods: This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg).

Results: The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P = .87). The proportions of subjects experiencing pain relief (P ≥ .48); reductions in migraine pain intensity (P ≥ .78); and relief from nausea, photophobia, or phonophobia (P ≥ .88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M = 2.6 vs M = 2.4, P = .81) and the mean number of rescue medications used (M = .11 vs M = .26, P = .32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n = 14 [44%]; 6 mg, n = 18 [56%], P = .60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events.

Conclusions: The 3-mg SC dose of sumatriptan in DFN-11 provided relief of migraine pain and associated symptoms comparable to a 6-mg SC dose of sumatriptan. Tolerability was similar with both study medications; DFN-11 treatment was associated with fewer triptan sensations than the 6-mg dose. DFN-11, with its 3-mg dose of sumatriptan, may be a clinically useful alternative to higher-dose autoinjectors.

Keywords: Episodic; Migraine; Rapidly-escalating; Subcutaneous; Sumatriptan; Treatment.

Figures

Fig. 1

Subject disposition

Fig. 2

Pain freedom at 30, 60, 90, and 120 min postdosea,b. Legend: SC, subcutaneous. aMean (SD) predose pain intensity average was 2.00 (.58). b1 subject randomized to 6 mg only treated 1 attack

Fig. 3

Pain relief at 30, 60, 90, and 120 min postdosea. Legend: SC, subcutaneous. a1 subject randomized to 6 mg only treated 1 attack

Fig. 4

Pain intensity at predose, 30, 60, 90, and 120 min postdosea,b,c. Legend: SC, subcutaneous. a1 subject randomized to 6 mg only treated 1 attack. bRepeated Measures ANOVA revealed an insignificant group and time interaction: F(2.43, 85.02)  =  .61, P  =  .78. cA significant main effect of time was found for pain intensity scores: F(2.43, 85.02)  =  .61, P  <  .001

Fig. 5

Proportions of subjects experiencing relief from symptoms associated with migraine at 60 min postdose.a Legend: SC, subcutaneous. a1 subject randomized to 6 mg only treated 1 attack. b3 mg n  =  8; 6 mg n  =  10. c3 mg n  =  9; 6 mg n  =  11. d3 mg n  =  10; 6 mg n  =  9