DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-FINDING STUDY OF RIZATRIPTAN (MK-462) IN THE ACUTE TREATMENT OF MIGRAINE

Rizatriptan (MK-462) is a potent 5HT(ID) receptor agonist. This multic enter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n=417) were treated with placebo (n=67), rizatriptan 2.5 mg (n=75), 5 mg (n=130), or rizatriptan 10 mg (n=145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test dr ug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2. 5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatrip tan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proport ion of patients reporting pain relief, i.e., a change in headache seve rity to ''no pain or mild pain'' at 2 h post-dose. The relationship wa s evident even at the first recorded timepoint, 30 min, and was statis tically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain r elief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21. 3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of p atients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatri ptan 10 mg was consistently more effective than 5 mg, although the dif ferences were not statistically significant. The most frequent clinica l adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.