Double-blind, placebo-controlled, dose-finding study of rizatriptan (MK-462) in the acute treatment of migraine.
Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, 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 drug 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, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to "no pain or mild pain" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief 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 patients 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. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.
Gijsman
H
H
Leiden University Hospital, Netherlands.
Kramer
M S
MS
Sargent
J
J
Tuchman
M
M
Matzura-Wolfe
D
D
Polis
A
A
Teall
J
J
Block
G
G
Ferrari
M D
MD
D000208:Acute Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D012044:Regression Analysis; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014363:Tryptamines
D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan