Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine.
; Schoenen, Jean ; et al
in Cephalalgia : An International Journal of Headache (2009), 29 Suppl 2
Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of ... [more ▼]
Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis. [less ▲]Detailed reference viewed: 19 (1 ULg)
No effect of eletriptan administration during the aura phase of migraine
; ; Schoenen, Jean et al
in European Journal of Neurology (2004), 11(10), 671-677
Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide ... [more ▼]
Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in >50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase. [less ▲]Detailed reference viewed: 20 (0 ULg)
Comparative efficacy of eletriptan and zolmitriptan in the acute treatment of migraine
; ; et al
in Cephalalgia : An International Journal of Headache (2003), 23(10), 942-952
Eletriptan 40 mg and 80 mg have shown greater efficacy in acute migraine than oral sumtriptan 100 mg and naratriptan 2.5 mg. This study continues the systematic series of active comparator trials in the ... [more ▼]
Eletriptan 40 mg and 80 mg have shown greater efficacy in acute migraine than oral sumtriptan 100 mg and naratriptan 2.5 mg. This study continues the systematic series of active comparator trials in the eletriptan clinical development programme. In a multicentre double-blind, double-dummy, parallel-groups trial, 1587 outpatients with migraine by IHS criteria were randomised in a 3: 3: 3: 1 ratio to eletriptan 80 mg, eletriptan 40 mg, zolmitriptan 2.5 mg or placebo. Of these, 1312 treated a single migraine attack and recorded baseline and outcome data to be included in the intention-to-treat population. The primary analysis was between eletriptan 80 mg and zolmitriptan. For the primary efficacy end-point of 2-h headache response, rates were 74% on eletriptan 80 mg, 64% on eletriptan 40 mg, 60% on zolmitriptan (P < 0.0001 vs. eletriptan 80 mg) and 22% on placebo (P < 0.0001 vs. all active treatments). Eletriptan 80 mg was superior to zolmitriptan on all secondary end-points at 1, 2 and 24 h, in most cases with statistical significance. Eletriptan 40 mg had similar efficacy to zolmitriptan 2.5 mg in earlier end-points, and significantly (P < 0.05) lower recurrence rate and need for rescue medication over 24 h. All treatments were well tolerated; 30-42% of patients on active treatments and 40% on placebo reported all-causality adverse events that were mostly mild and transient. On patients' global ratings of treatment, both eletriptan doses scored significantly better than zolmitriptan. [less ▲]Detailed reference viewed: 43 (1 ULg)
A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study.
; ; et al
in Cephalalgia : An International Journal of Headache (2001), 21(2), 120-8
This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg ... [more ▼]
This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between two and six migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from three to two in the ASA group and from three to one in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature. [less ▲]Detailed reference viewed: 13 (0 ULg)
Zolmitriptan, a 5-HT1B/1D receptor agonist for the acute oral treatment of migraine: a multicentre, dose-range finding study.
; ; et al
in European Journal of Neurology (1998), 5(6), 535-543
Zolmitriptan is a selective 5-HT1B/1D receptor agonist for acute oral migraine therapy. This randomized, placebo-controlled, parallel-group study investigated the efficacy and tolerability of oral ... [more ▼]
Zolmitriptan is a selective 5-HT1B/1D receptor agonist for acute oral migraine therapy. This randomized, placebo-controlled, parallel-group study investigated the efficacy and tolerability of oral zolmitriptan (5, 10, 15 and 20 mg) in the treatment of single acute migraine attacks. Of 1181 patients randomized, 840 were evaluable for the primary efficacy analysis. Headache response rates (a reduction in headache intensity from severe or moderate at baseline to mild or no pain at 2 hours post-treatment) were similar across the zolmitriptan dose groups (66%, 71%, 69% and 77% for 5 mg, 10 mg, 15 mg and 20 mg, respectively) and were significantly higher than that for placebo (19%; all groups P < 0.001). A headache response was reported at 1 hour by 40-50% of zolmitriptan recipients (16% placebo). At 2 hours post dose, 39-47% of zolmitriptan-treated patients were pain-free, compared with 1% of placebo recipients. Headache recurrence occurred in 21-29% (upper 95% CI 37.1) of zolmitriptan-treated patients and in 65% (95% CI 38.3, 85.8) of placebo recipients. Zolmitriptan was well tolerated at each dose. The most commonly reported adverse events were asthenia, dizziness, paraesthesia and feelings of heaviness. Most adverse events were of mild or moderate intensity and were transient. The frequency of adverse events was dose-related. Although, zolmitriptan 5 mg exhibited the most favourable efficacy and tolerability profile, the dose response data suggest that lower doses would also offer significant efficacy. Copyright 1998 Lippincott Williams & Wilkins [less ▲]Detailed reference viewed: 15 (1 ULg)
Migraine and cluster headache--their management with sumatriptan: a critical review of the current clinical experience.
; ; Schoenen, Jean et al
in Cephalalgia : An International Journal of Headache (1995), 15(5), 337-57
Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which mediates constriction of certain large cranial blood vessels and/or inhibits the release of vasoactive neuropeptides from ... [more ▼]
Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which mediates constriction of certain large cranial blood vessels and/or inhibits the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater following activation of the trigeminovascular system. The mode of action of this drug in migraine and cluster headache is discussed. On the basis of a detailed review of all published trials and available data from post-marketing studies, the efficacy, safety, tolerability and the place of oral and subcutaneous sumatriptan in the treatment of both conditions are assessed. A number of double-blind clinical trials have demonstrated that sumatriptan 100 mg administered orally is clearly superior to placebo in the acute treatment of migraine headache and achieves significantly greater response rates than ergotamine or aspirin. In other studies, 70 to 80% of patients receiving sumatriptan 6 mg sc experienced relief of migraine headaches by 1 or 2 h after administration, and patients consistently required less rescue medication for unresolved symptoms. Sumatriptan was also effective in relieving associated migraine symptoms like nausea and vomiting. Sumatriptan was equally effective regardless of migraine type or duration of migraine symptoms. Overall, approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache usually within 24 h, effectively treated by a further dose of this drug. In 75% of patients with cluster headache treated with sumatriptan 6 mg sc, relief was achieved within 15 min. Based on pooled study data, sumatriptan is generally well tolerated and most adverse events are transient. Adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. With the subcutaneous injection, injection site reactions occur in approximately 30%. Chest syumptoms are reported in 3 to 5% but have been associated with myocardial ischaemia only in rare isolated cases. The recommended dosage of sumatriptan at the onset of migraine symptoms is 100 mg orally or 6 mg subcutaneously. The recommended dosage for cluster headache is 6 mg sumatriptan sc. Sumatriptan must not be given together with vasoconstrictive substances, e.g., ergotamines, or with migraine prophylactics with similar properties, e.g., methysergide. Sumatriptan should not be given during the migraine aura. It is contraindicated in patients with ischaemic heart disease, previous myocardial infarction, Prinzmetal (variant) angina and uncontrolled hypertension. [less ▲]Detailed reference viewed: 27 (0 ULg)