Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from
sumatriptan and other
indole derivatives used or being developed for the treatment of acute
migraine. In a multinational double-blind randomized parallel-groups dose-finding trial,
alniditan was given subcutaneously in hospital to patients with
migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection,
headache was absent or mild in 83% and 82% of patients receiving
alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from
headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing
alniditan dose, and there was a dose-dependent reduction in
headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and
headache recurred within 24 h in only 16% of the patients who initially responded to
alniditan 1.4 mg, significantly less than for placebo (p = 0.018).
Alniditan was superior to placebo in reducing the associated symptoms of
nausea,
phonophobia and
photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the
drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving
alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that
alniditan 1.4 mg sc may have advantages over
sumatriptan 6 mg sc in providing complete relief from acute
migraine headache, and may be associated with fewer
headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of
alniditan in acute
migraine.