Early clinical experience with subcutaneous naratriptan in the acute treatment of migraine: a dose‐ranging study

Abstract

Naratriptan is a novel, potent agonist at the 5HT1B/1D receptor. A total of 335 migraine patients were treated in this randomized, double-blind, placebo-controlled, dose-ranging, in-clinic study, to evaluate the efficacy, safety and tolerability of five doses of subcutaneous (sc) naratriptan (0.5, 1, 2.5, 5 or 10 mg) in comparison with sc sumatriptan (6 mg) and placebo in the acute treatment of a moderate/severe migraine attack. Headache relief [reduction of headache severity from moderate or severe (grade 2/3) to mild or none (grade 1/0)] at 1 and 2 h after each dose, was reported by a statistically significantly higher proportion of patients for all doses of sc naratriptan and sc sumatriptan (6 mg) than for placebo. The percentages of patients with headache relief at 2 h post-dose were: naratriptan (0.5 mg) 65%, (1 mg) 75%, (2.5 mg) 83%, (5 mg) 94% and (10 mg) 91%; sumatriptan (6 mg) 89%; placebo 41%, (P < 0.005). The earliest report of a statistically significant difference compared with placebo for the times assessed was with sc naratriptan (10 mg) at 10 min post-dose (P = 0.023). The percentages of patients reporting adverse events were dose-related; sc naratriptan (0.5 mg) 33%, (1 mg) 29%, (2.5 mg) 43%, (5 mg) 59% and (10 mg) 71%; sc sumatriptan 53%; placebo 22%. There were no clinically significant changes in electrocardiogram (ECG), vital signs or laboratory parameters. Systemic exposure increased proportionally to the dose, the absorption of sc naratriptan was rapid (tmax = 10 min) and the half-life was 5 h. In conclusion, sc naratriptan was an effective and well-tolerated acute treatment for migraine. Copyright 1998 Lippincott Williams & Wilkins

Sumatriptan (Subcutaneous Route of Administration) for Acute Migraine Attacks in Adults

“…• Sumatriptan 6 mg versus placebo (Akpunonu 1995;Bates 1994;Bousser 1993;Cady 1991 Study 1 and Study 2;Cady 1993;Cady 1998;Dahlof 1998;Diener 1999;Diener 2001;Facchinetti 1995;Ferrari 1991;Gross 1994;Henry 1993;Jensen 1995;Mathew 1992;Mushet 1996 • Sumatriptan 6 mg versus subcutaneous naratriptan 0.5 mg (Dahlof 1998). …”

“…We considered no studies to be at high risk of bias from random sequence generation, allocation concealment, or blinding. Fifteen studies (Akpunonu 1995;Bates 1994;Bousser 1993;Cady 1993;Dahlof 1992;Dahlof 1998;Diener 1999;Gross 1994;Henry 1993;Mathew 1992;Mushet 1996 Study 1 and Study 2;Sang 2004;Schulman 2000;Thomson 1993) did not include 50 or more participants in each treatment arm and we therefore considered them to be at high risk of bias from their size.…”

“…Sumatriptan 6 mg versus placebo: Thirteen studies (2522 participants) provided data (Dahlof 1998;Diener 1999;Diener 2001;Facchinetti 1995;Mathew 1992 • The proportion of participants pain-free at two hours with sumatriptan 6 mg was 59% (799/1351; range 48% to 76%).…”

“…Sumatriptan 6 mg versus placebo: Five studies (987 participants) provided data for the use of rescue medication up to 24 hours after initial dosing (Cady 1998;Dahlof 1998;Diener 1999;Diener 2001;Schulman 2000).…”

“…Four studies (Dahlof 1998;Diener 1999;Diener 2001;S2BL99) provided data comparing sumatriptan with an active comparator for the use of rescue medication up to 24 hours after initial dosing. None of these studies used comparable active comparators so no pooled analysis could be carried out.…”