Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. METHODS: Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005) and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack, 7.1% of patients in the almotriptan group experienced adverse events compared to 5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.     

Almotriptan increases sustained pain-free outcomes in acute migraine: results from three controlled clinical trials

OBJECTIVE: Evaluate the effect of almotriptan on sustained pain-free outcome in patients with acute migraine. METHODS: Three randomized, double-blind, placebo-controlled trials of almotriptan for the treatment of acute migraine were examined. Two trials evaluated almotriptan 6.25 mg and 12.5 mg, and the third evaluated almotriptan 12.5 mg and sumatriptan 100 mg. Patients aged 18 to 65 years were instructed to take 1 dose of study medication at the onset of a moderate-to-severe migraine headache. A second dose was allowed for relapse. Sustained pain-free was defined as a decrease in pain severity from moderate or severe at baseline to no pain at 2 hours postdose and without relapse or the use of escape medication between 2 and 24 hours. RESULTS: A total of 1791 adult migraine sufferers were studied. The proportion of patients achieving a sustained pain-free state was significantly (P<.05) higher in the almotriptan 6.25-mg (21.7% to 22.5%) and 12.5-mg (24.6% to 27.6%) groups than in the placebo group (7.5% to 12.1%). The proportion of patients achieving a sustained pain-free state was comparable between almotriptan 12.5 mg (24.6%) and sumatriptan 100 mg (28.5%) and significantly (P<.05) greater than with placebo (12.1%). Among patients with severe baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.05) with almotriptan 12.5 mg (17.3% to 20.9%) than with placebo (3.1% to 3.2%). Among those with moderate baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.01) with almotriptan 12.5 mg (31.3% to 32.0%) than with placebo (10.2% to 16.1%). CONCLUSIONS: Almotriptan 12.5 mg is significantly better than placebo and comparable to sumatriptan 100 mg for achieving a sustained pain-free state.     

Almotriptan Increases Pain-Free Status in Patients With Acute Migraine Treated in Placebo-Controlled Clinical Trials

Objectives.—Evaluate the efficacy of a single oral dose of almotriptan in achieving pain-free status during treatment of acute migraine attacks.
Methods.—This pooled analysis (N=1321) used data from two randomized, placebo-controlled, phase III trials (studies A and B) to determine the proportion of patients with migraine achieving pain-free status 2 hours after a single oral dose of study medication (almotriptan or placebo). Pain was assessed using a 4-point integer scale (0=no headache, 3=severe headache), and recorded in a patient self-assessment booklet.
Results.—The proportion of patients pain-free at 2 hours after study medication was significantly greater with almotriptan 6.25 mg (both studies P ≤.002) and almotriptan 12.5 mg (both studies P ≤.001) than with placebo. In study A, 11.6% of patients taking almotriptan 12.5 mg versus 2.5% of patients receiving placebo were pain-free at 1 hour ( P =.016). At 1.5 hours, 26.8% of patients taking almotriptan 12.5 mg versus 8.8% receiving placebo ( P =.001) were pain-free, and at 2 hours, 38.4% on almotriptan versus 11.3% on placebo were pain-free ( P <.001). In study B, 23.8% of patients taking almotriptan 12.5 mg were free from pain at 1.5 hours versus 10.2% receiving placebo ( P <.001). At 2 hours, 39.2% taking almotriptan 12.5 mg versus 15.3% receiving placebo were pain-free ( P <.001). Increases in pain-free status with almotriptan generally occurred in a dose-dependent manner.
Conclusion.—Compared with placebo, almotriptan 12.5 mg significantly increases the proportion of patients who are pain-free by as early as 1 hour, and consistently by 1.5 hours, after a single dose.     

Early intervention with almotriptan improves sustained pain-free response in acute migraine

OBJECTIVE: To determine whether treatment of migraine with almotriptan, when pain intensity is mild, improves 1- and 2-hour pain-free and sustained pain-free rates compared with treatment when pain intensity is moderate or severe. METHODS: This was a post hoc analysis derived from an open-label, multicenter, long-term study of the safety, tolerability, and efficacy of almotriptan 12.5 mg. Patients who met International Headache Society criteria for migraine with or without aura were eligible. Patients were instructed to take a single dose of almotriptan 12.5 mg at the onset of a migraine attack. Rescue medication could be taken if migraine pain had not disappeared at 2 hours. A second dose of almotriptan 12.5 mg could be taken if head pain recurred within 24 hours of the initial dose. Patients reported the intensity of pain at baseline and at 1 and 2 hours postmedication using a 4-point scale: no pain, mild, moderate, or severe pain. They also reported recurrence of pain (return of moderate or severe pain within 2 to 24 hours of taking the study medication) and use of rescue medication. Rescue medication consisted of supplemental analgesics taken for pain relief at 2 to 24 hours postdose. Ergotamines and other 5-HT1B/1D agonists were excluded as rescue medications. Based on these patient-reported end points, sustained pain-free rates, defined as pain-free at 2 hours with no recurrence from 2 to 24 hours and no use of rescue medication, were calculated. RESULTS: A higher proportion of migraine attacks of mild intensity were pain-free at 1 hour (35.3%) compared with attacks of moderate or severe intensity (7.5%) (P <.001). Two-hour pain-free rates also were significantly higher with mild intensity pain (76.9%) compared to moderate or severe intensity (43.9%) (P <.001). In addition, recurrence rates and use of rescue medication were reduced when attacks were treated during mild pain. Recurrence was 12.9% for mild pain versus 25.0% for moderate or severe pain (P <.001), and use of rescue medication was 9.4% for mild pain versus 17.2% for moderate or severe pain (P <.001). Sustained pain-free rates were nearly twice as high when attacks were treated during mild intensity pain (66.6%) compared with attacks treated during moderate or severe pain (36.6%) (P <.001). CONCLUSION: Treatment with almotriptan 12.5 mg during migraine attacks of mild pain intensity improves 1- and 2-hour pain-free and sustained pain-free responses.     

Meta-analysis examining the efficacy and safety of almotriptan in the acute treatment of migraine

OBJECTIVE: To evaluate the comparative efficacy and safety of oral almotriptan in treating acute migraine attacks. BACKGROUND: Almotriptan is an oral selective sertonin(1B/1D) receptor agonist (triptan) with a high bioavailability and short half-life, developed for the treatment of migraine. In recent years, a number of randomized controlled trials have been published examining the efficacy and safety of almotriptan in the acute treatment of migraine. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) using a random-effects model to estimate the pooled rate ratios (RRs) and 95% confidence intervals (95%CI) for the proportions of patients achieving headache relief and pain-free responses at 1 or 2 hours post-dose, sustained pain-free response at 2-24 hours post-dose, and safety outcomes (proportions of patients experiencing any adverse events, dizziness, somnolence, asthenia, and chest tightness) comparing almotriptan against placebo, other triptans, and different dosages of almotriptan. Absolute rate differences (ARDs) for 2-hour headache relief, pain free, and sustained pain free responses between almotriptan and placebo were also calculated. RESULTS: Eight RCTs involving 4995 patients were included in the analysis. Almotriptan 12.5 mg was significantly more effective than placebo for all efficacy outcomes (RRs ranged from 1.47 to 2.15; ARDs ranged from 0.01 to 0.28) and there were no significant differences in any of the safety outcomes. There were also no significant differences in efficacy outcomes comparing almotriptan 12.5 mg against sumatriptan 100 mg and zolmitriptan 2.5 mg, but almotriptan 12.5 mg was associated with significantly fewer adverse events than sumatriptan 100 mg (RR: 0.39, 95%CI: 0.23, 0.67). However, there was no significant difference between almotriptan and sumatriptan in terms of clinically important adverse effects, such as dizziness, somnolence, asthenia, and chest tightness. Almotriptan 12.5 mg was significantly less effective than almotriptan 25 mg for 1-hour pain-free response (RR: 0.45, 95%CI: 0.21, 0.95), but associated with significantly fewer patients experiencing adverse events (RR: 0.61, 95%CI: 0.41, 0.91) than almotriptan 25 mg. CONCLUSIONS: Almotriptan 12.5 mg is an effective treatment for acute attacks of migraine, in particular, it has been found to be as effective as sumatriptan 100 mg and zolmitriptan 2.5 mg. The risk of adverse events associated with almotriptan 12.5 mg was similar to placebo and significantly lower than sumatriptan 100 mg. Further research is required to assess the comparative efficacy of almotriptan against other triptans.     

A review of the effects of almotriptan and other triptans on clinical trial outcomes that are meaningful to patients with migraine

BACKGROUND: Traditional end points in clinical trials of migraine therapy, such as 2-hour pain response, may not fully address the outcomes patients consider most important: rapid and sustained freedom from pain over 24 hours, and a low, placebo-like incidence of adverse events. A composite efficacy measure such as the sustained pain-free rate (no pain by 2 hours after dosing, no recurrence, no use of rescue medication from 2 to 24 hours after dosing) may be more appropriate. OBJECTIVE: Clinically relevant differences between almotriptan and other triptans were reviewed in the context of the attributes of acute migraine treatment that patients consider most important. METHODS: This review was based on published reports of open-label and placebo-controlled clinical trials of almotriptan, results of a survey concerning the attributes patients consider most important in a migraine medication, and a published meta-analysis of 53 placebo-controlled clinical trials of triptans involving >24,000 patients. RESULTS: Almotriptan was effective and well tolerated in the placebo-controlled clinical trials; results of the 6- and 12-month open-label studies supported its good tolerability profile. A respective 87% and 86% of respondents to the patient survey indicated that they considered complete freedom from pain and no recurrence among the most important attributes of migraine treatment, both of which are included in the sustained pain-free rate. In the meta-analysis, almotriptan had a favorable efficacy and tolerability profile compared with other triptans, particularly with respect to sustained pain-free rate, which was significantly higher with almotriptan 12.5 mg compared with sumatriptan 100 mg (25.9% vs 20.0%, respectively; P < 0.05). In addition, the placebo-subtracted rate of adverse events was significantly lower with almotriptan compared with sumatriptan (1.8% vs 4.4%, respectively; P < 0.05). Results of a head-to-head placebo-controlled trial of almotriptan 12.5 mg and sumatriptan 100 mg supported the balance of efficacy and tolerability observed for almotriptan in the meta-analysis. CONCLUSIONS: Data from clinical trials suggest that almotriptan is effective and well tolerated in the treatment of acute migraine pain. Based on a sustained pain-free rate that is among the highest and an adverse-event rate that is among the lowest for the triptans, almotriptan represents a therapeutic option for the initial treatment of acute migraine with or without aura.     

Meta-analysis of the efficacy and safety of zolmitriptan in the acute treatment of migraine

OBJECTIVE: To assess the relative efficacy and safety of zolmitriptan in the treatment of acute migraine attacks. BACKGROUND: Zolmitriptan is a second-generation triptan developed for the treatment of migraine. Numerous randomized controlled trials (RCTs) have been carried out to compare different dosages and formulations of zolmitriptan against other treatments for acute migraine. METHODS: Random effects meta-analysis of 24 RCTs, including 15,408 patients suffering from acute migraine attacks. Subgroup analyses compared differences in response between different dosages and formulations of zolmitriptan, and other triptan comparators. RESULTS: Zolmitriptan 2.5 mg tablet was found to be as effective as almotriptan 12.5 mg, eletriptan 40 mg, sumatriptan 50 mg and 100 mg and more effective than naratriptan 2.5 mg in terms of 2-hour pain-free rates. Likewise, zolmitriptan 5 mg tablet was as effective as sumatriptan 50 mg and 100 mg in 2-hour pain-free rates. Compared against zolmitriptan 2.5 mg tablet, eletriptan 80 mg was more effective in achieving headache relief, pain-free and sustained pain-free responses, and rizatriptan 10 mg was more effective in terms of sustained pain-free rates. Zolmitriptan 2.5 mg tablet was associated with a lower risk of adverse events than eletriptan 80 mg but higher risk than naratriptan 2.5 mg and rizatriptan 10 mg. Zolmitriptan 5 mg tablet was superior to zolmitriptan 2.5 mg tablet in achieving 1- and 2-hour pain-free response. There were no significant differences in 1- and 2-hour headache relief and adverse event rates between the different formulations of zolmitriptan 2.5 mg. CONCLUSIONS: Zolmitriptan 2.5 mg tablet is an effective treatment for acute attacks of migraine showing similar efficacy to almotriptan 12.5 mg, eletriptan 40 mg, and sumatriptan 50 mg, and being more effective than naratriptan 2.5 mg in terms of pain-free response at 2 hours post dose. Zolmitriptan 2.5 mg tablet was also as effective as rizatriptan 10 mg in terms of headache relief and pain-free response but less effective in terms of sustained pain-free response.     

Early intervention with almotriptan: results of the AEGIS trial (AXERT Early Migraine Intervention Study)

OBJECTIVE: To evaluate prospectively the efficacy and safety of almotriptan 12.5 mg as compared to placebo when administered within 1 hour of headache pain onset for the acute treatment of 3 migraine headaches. BACKGROUND: Although clinical trials have reported improved outcomes when triptans were used early or to treat mild pain, acceptance of this treatment strategy has been hampered by both efficacy and tolerability issues. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group trial, patients with IHS-migraine were randomized in a 1:1 ratio to treat 3 consecutive migraine attacks with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of headache pain of any intensity, within 1 hour of onset, and to record their symptoms at multiple time points during their headaches using a personal digital assistant. Clinical trial efficacy results for the first study headache and safety data for the entire study are presented. RESULTS: A total of 378 patients were randomized, 189 to each group; 162 almotriptan-treated patients, and 155 placebo-treated patients were evaluable for efficacy. Almotriptan treatment, compared to placebo, resulted in a significantly greater proportion of patients achieving 2-hour pain free (37.0% vs 23.9%, P= .010), 2-hour pain relief (72.3% vs 48.4%, P < .001) and sustained pain free (24.7% vs 16.1%, P= .040). Significant differences in pain free (P= .026) and pain relief (P= .019) between almotriptan and placebo also were observed at 1 hour. At 2 to 4 hours and 4 to 24 hours after treatment, the mean intensity of phonophobia and photophobia were significantly lower in the patients treated with almotriptan compared to the placebo-treated patients. A greater proportion of patients treating with almotriptan versus placebo reported normal functionality within 2 hours postdose (54.4% vs 38.1%, P= .007) and 4 hours postdose (74.5% vs 54.3%, P < .001). The percentage of patients experiencing 1 or more treatment-emergent adverse events (AE) was 9.8% for almotriptan and 6.4% for placebo. The only treatment-emergent AEs that occurred with a frequency of at least 1% (equivalent to 2 or more patients) in the almotriptan and placebo groups, respectively, were somnolence (1.1% and 2.3%), nausea (1.1% and 1.7%), vomiting (1.1% and 0.6%), and fatigue (1.1% and 0%). CONCLUSION: Treatment with almotriptan within 1 hour of migraine onset resulted in significantly better clinical outcomes than placebo and tolerability similar to placebo. Acute medications, such as almotriptan, that are both effective and well tolerated may encourage patients to access acute treatment earlier.     

Efficacy and tolerability of sumatriptan tablets in a fast-disintegrating, rapid-release formulation for the acute treatment of migraine: results of a multicenter, randomized, placebo-controlled study

BACKGROUND: Sumatriptan tablets have been developed in a fast-disintegrating, rapid-release formulation designed to facilitate tablet disintegration and drug dispersion and to potentially mitigate the effects of gastric stasis that can accompany migraine. OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of sumatriptan 50- and 100-mg tablets in a fast-disintegrating, rapid-release formulation compared with those of placebo in patients with migraine. METHODS: This clinical trial had a randomized, double-blind, placebo-controlled, parallel-group design. Exclusion criteria included >6 migraines monthly during either of the 2 months before screening; uncontrolled hypertension; suspected or confirmed cardiovascular or cerebrovascular disease; and ophthalmic, basilar, or hemiplegic migraine. Sumatriptan 50 and 100 mg and placebo were taken on an outpatient basis during the mild-pain phase of a single migraine attack. Patients recorded details of the treated migraine on a diary card and rated pain severity immediately before dosing and 30 minutes, 45 minutes, 1 hour, and 2 hours after dosing using a 4-point scale (from 0 = none to 3 = severe). The primary efficacy end point was the proportion of patients who were pain free 2 hours after dosing. Additional efficacy end points were the proportion of patients who were pain free at 30 minutes, 45 minutes, and 1 hour after dosing; the proportion who were migraine free through 2 hours after dosing; and the proportion with a sustained pain-free response. RESULTS: Patients' mean age ranged from 39.7 to 41.5 years across the 3 groups, and the majority were women (79.7%-85.9%) and white (98.7%-100%). One hundred thirty-seven patients received sumatriptan 50 mg, 142 sumatriptan 100 mg, and 153 placebo. In the intent-to-treat population (n = 432), 51.1% of patients who received sumatriptan 50 mg and 66.2% of patients who received sumatriptan 100 mg were pain free 2 hours after dosing, compared with 19.6% of the placebo group (P < 0.001, each sumatriptan dose vs placebo). In an exploratory analysis, the 2-hour pain-free rate with sumatriptan 100 mg was significantly better than that with sumatriptan 50 mg (P = 0.007). Significantly more patients who received sumatriptan 100 mg were pain free compared with placebo at 30 minutes (P < 0.01), 45 minutes (P < 0.001), and 1 hour after dosing (P < 0.001); similar pain-free results were observed in patients who received sumatriptan 50 mg at 45 minutes (P < 0.05) and 1 hour (P = 0.01). In the per-protocol population (n = 313), pain-free efficacy 2 hours after dosing was 52.7% with sumatriptan 50 mg and 74.8% with sumatriptan 100 mg, compared with 21.0% with placebo (P < 0.001, each sumatriptan dose vs placebo). These rates were greater than those in the overall study population, approximately 12.0% of whom treated moderate or severe pain. The only drug-related adverse events reported in >/=3% of patients in any treatment group were nausea and vomiting (<1%, 5%, and 2% in the sumatriptan 50 and 100 mg and placebo groups, respectively), chest symptoms (2%, 3%, and 0%), and malaise and fatigue (1%, 3%, and <1%). No serious adverse events were reported. CONCLUSIONS: In this study, sumatriptan tablets in a fast-disintegrating, rapid-release oral formulation provided pain-free efficacy in the acute treatment of migraine. Efficacy was maximized with the 100-mg dose compared with the 50-mg dose, and by treating early when pain was mild. In the intent-to-treat population, 51.1% of patients who received sumatriptan 50 mg and 66.2% of those who received sumatriptan 100 mg were pain free 2 hours after dosing. In the per-protocol population, 3 of 4 patients taking the 100-mg tablets for mild pain within 1 hour of its onset were pain free at 2 hours. Sumatriptan tablets were generally well tolerated.     

Use of rescue medication in trials of almotriptan versus placebo in the treatment of acute migraine

BACKGROUND: Almotriptan malate is a recently marketed triptan for the treatment of acute migraine. Results from controlled clinical trials demonstrate efficacy superior to placebo and an adverse event rate comparable to that with placebo. OBJECTIVE: The goal of this study was to assess the effect of oral almotriptan on the use of rescue medication in the treatment of acute migraine attacks. METHODS: Three Phase II and III, placebo-controlled, randomized, double-blind studies of almotriptan used as the basis for regulatory approval of the drug were included in the analysis. Two studies (1 single dose, 1 multiple dose) assessed almotriptan 6.25 mg and 12.5 mg and a third compared almotriptan 12.5 mg and sumatriptan 100 mg. Primary results from all 3 trials were previously published. Rescue medication was permitted if migraine pain had not decreased to mild severity or to no pain at 2 hours after study medication. The primary end point of this analysis was use of rescue medication. RESULTS: A total of 1777 patients were included in the analysis. Mean patient age ranged from 39.4 to 44.0 years; approximately 87% were women, and >98% were white. Patients were well matched for demographic characteristics. Overall, use of rescue medication was significantly lower with almotriptan 6.25 mg and 12.5 mg compared with placebo (P < or = 0.05 for each group). No significant difference was noted between the almotriptan 12.5-mg and sumatriptan 100-mg groups. In 2 of the studies, patients with moderate or severe baseline pain used significantly less rescue medication in the almotriptan groups compared with placebo. CONCLUSIONS: Oral almotriptan 6.25 mg or 12.5 mg significantly reduced use of rescue medication compared with placebo among patients with acute migraine. Use of rescue medication was comparable with almotriptan 12.5 mg and sumatriptan 100 mg.     

Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials

A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine. As early as 30 min after dosing, almotriptan 12.5 mg was significantly more effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free (2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for placebo. All almotriptan dosages were significantly more effective than placebo in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained pain relief up to 24 h (P < 0.05). The incidence of adverse events after almotriptan 6.25 mg and 12.5 mg was not significantly different from that of placebo. This meta-analysis confirms the findings of individual clinical trials, while demonstrating for the first time, significant pain-free efficacy at 30 min compared with placebo.     

Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study

OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, versus placebo for early intervention while head pain was mild in patients with disabling migraine. METHODS: A post hoc analysis was performed in a subgroup of patients from a large, randomized, placebo-controlled study of patients with disabling headache who treated while pain was mild. Pain-free response 2 and 4 hours postdose, headache recurrence, and safety were examined. Significance tests were performed only for the first-treated attacks. RESULTS: Twenty-six patients with disabling headache treated 46 mild and 166 moderate or severe headaches. For the first-treated headaches while pain was mild, pain-free rates were significantly higher for sumatriptan than placebo 4 hours postdose (78% versus 0%, P =.02), but not 2 hours postdose (52% versus 0%, P =.22). Across all headaches treated while pain was mild, pain-free responses were higher for sumatriptan than placebo 4 hours (85% versus 17%) and 2 hours (50% versus 0%) postdose compared with placebo. When the same patients treated headaches while pain was moderate or severe, pain-free rates were lower than that reported for treatment during mild pain. There was a trend toward lower headache recurrence in headaches treated while pain was mild compared with moderate or severe pain (13% versus 18%). No drug-related adverse events were reported in the headaches treated while pain was mild. CONCLUSIONS: Patients with disabling migraine may benefit from early intervention with sumatriptan, 50 mg, while pain is mild.     

Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg

OBJECTIVE: To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan 100 mg. Background.-Eletriptan 80 mg has demonstrated significantly greater efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies. Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100 mg in one previous trial. METHODS: Two thousand one hundred thirteen patients with a diagnosis of migraine according to International Headache Society criteria were randomized using a double-blind, double-dummy, parallel-group design, and treated for a single migraine attack with either eletriptan 40 mg, sumatriptan 100 mg, or placebo. The primary endpoint was 2-hour headache response. Secondary endpoints included headache response rates at 1 hour, pain-free rates, absence of associated symptoms, functional response at 1 and 2 hours, and sustained headache response. RESULTS: Headache response rates at 2 hours postdose were significantly higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (59%; P <.001) and placebo (26%; P <.0001). Eletriptan 40 mg consistently showed significant (P <.01) efficacy over sumatriptan 100 mg across secondary clinical outcomes, including 1-hour headache response; 2-hour pain-free response; absence of nausea, photophobia, and phonophobia; functional improvement; use of rescue medication; treatment acceptability; and sustained headache response (P <.05). Overall, treatment-related adverse events were low, nausea being the only adverse event with an incidence of 2% or higher (4.9% with eletriptan, 4.2% sumatriptan, 2.8% placebo). CONCLUSION: This trial confirmed that eletriptan 40 mg offers superior efficacy in treating migraine pain and associated symptoms and in restoring patient functioning when compared with sumatriptan 100 mg.     

A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine

OBJECTIVE: Evaluate the long-term tolerability of almotriptan 12.5 mg for the treatment of acute migraine attacks occurring over a 6-month period. BACKGROUND: Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular selectivity for meningeal arteries and has demonstrated efficacy for the treatment of acute migraine in short-term controlled trials. METHODS: This was a 6-month open-label study. Adults (18 years of age or older) were required to have a diagnosis of acute migraine with or without aura (according to the diagnostic criteria of the International Headache Society), a history of at least 1 year of moderate-to-severe migraine pain with at least two and a maximum of six migraines per month, and at least 24 hours of freedom from head pain between attacks. Patients were instructed to take a single 12.5-mg dose of almotriptan at the onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape medication could be taken; if relapse occurred in less than 24 hours, a second 12.5-mg dose could be taken. Tolerability was assessed from the nature and incidence of all adverse events, and efficacy was assessed according to the end point of pain relief 2 hours following almotriptan administration. RESULTS: Of 585 patients treated, 582 were included in the intent-to-treat population. The most frequent drug-related adverse events were nausea (3.1%) and dizziness (2.4%). No serious drug-related adverse events were reported, and no deaths occurred. Adverse events led to discontinuation of treatment in 36 patients (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six percent of patients achieved pain relief at 2 hours for all attacks treated, and 49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and pain-free rates were higher among those with moderate baseline pain. CONCLUSIONS: When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and effective for the long-term treatment of acute migraine.     

Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets

BACKGROUND: The gastric stasis that commonly accompanies migraine headache may impair absorption of conventional oral tablets in the stomach. A fast-disintegrating/rapid-release formulation of sumatriptan has been developed to enhance tablet disintegration and drug dispersion and potentially improve absorption. OBJECTIVE: Two studies were conducted comparing the time to onset of relief from moderate or severe migraine pain with the fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100 mg and placebo. METHODS: These were 2 identically designed randomized, double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was taken on an outpatient basis to treat a single moderate or severe migraine attack. Using a personal digital assistant, patients recorded the time of dosing and the time at which pain severity reached none or mild (ie, pain relief) or none (ie, pain free) in real time so that the time to onset of relief could be measured as a continuous variable. Onset of relief was defined as the earliest time point at which a statistically significant difference in pain relief compared with placebo was achieved and maintained through 2 hours after dosing. Before dosing and at pre-determined time points after dosing, patients also provided an assessment of migraine pain as none, mild, moderate, or severe. At a clinic visit within 1 week after treatment of the migraine attack, patients were queried about adverse events. For each adverse event, investigators recorded whether study medication was considered the cause. Data analyses were undertaken for each study individually and, in post hoc analyses of the primary and key secondary end points, on pooled data from both studies. RESULTS: The 2 studies comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan 100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8 years across treatment groups, and most patients were female (83%-87%) and white (92%-93%). In the analysis of pooled data, sumatriptan tablets provided significantly more effective pain relief compared with placebo as early as 20 minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing with the 50-mg dose (P < or = 0.05). Similar results were observed for the individual studies: in study 1, sumatriptan tablets were significantly more effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). The cumulative percentages of patients with a pain-free response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the individual studies, significantly more patients receiving either sumatriptan dose were migraine free 2 hours after dosing and had sustained pain relief and a sustained pain-free response over 24 hours compared with placebo (P < or = 0.001, both sumatriptan doses vs placebo). The only drug-related adverse events reported in >2% of patients in any treatment group in either study were nausea (both studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia (study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo). CONCLUSIONS: In these studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation were effective for the acute treatment of moderate to severe migraine pain, were generally well tolerated, and achieved an onset of pain relief as early as 20 minutes for 100 mg and as early as 30 minutes for 50 mg.     

Sumatriptan and naproxen sodium for the acute treatment of migraine

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine. BACKGROUND: The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multi-mechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets were encapsulated in order to achieve blinding of the study. RESULTS: In the sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), and versus placebo (38%; P= .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common. CONCLUSIONS: This is among the first prospective studies to demonstrate that multi-mechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine. This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy.     

Almotriptan Reduces the Incidence of Migraine-Associated Symptoms: A Pooled Analysis

Objectives.—Evaluate the reduction in migraine-associated symptoms after administration of a single oral dose of almotriptan.
Methods.—This pooled analysis (N=1773) used data from three randomized, placebo-controlled, phase III trials (studies A, B, and C) to determine the incidence of migraine-associated symptoms (defined as nausea, vomiting, photophobia, and phonophobia) 2 hours after a single oral dose of study medication (almotriptan, sumatriptan, or placebo). Outcome data was extracted from studies A and B for placebo and the almotriptan 6.25-mg and 12.5-mg groups, and from study C for placebo, almotriptan 12.5-mg, and sumatriptan 100-mg groups.
Results.—The incidence of nausea, photophobia, and phonophobia at 2 hours after dosing with study medication was significantly reduced (all P  < .05) with almotriptan 6.25 mg or 12.5 mg compared with placebo. The percentage of patients with vomiting was lower with both doses of almotriptan in studies A and B compared with placebo, although differences were significant only for the 6.25-mg dose in study A ( P  < .001). For study C, the incidence of nausea, vomiting, photophobia, and phonophobia was similar for almotriptan and sumatriptan and lower than with placebo at 2 hours after dosing. Significant reductions (all P  < .05) versus placebo were observed in the incidence of vomiting and phonophobia with almotriptan 12.5 mg, and photophobia and phonophobia with sumatriptan 100 mg.
Conclusion.—Almotriptan provides relief from migraine-associated symptoms of nausea, vomiting, photophobia, and phonophobia, and thus represents an attractive treatment option for a wide spectrum of migraine symptomatology.     

Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial

Objectives.— To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents. Patients and Methods.— In this double‐blind, placebo‐controlled, parallel‐group, multicenter trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per International Headache Society criteria) were randomized to treat one migraine headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours after dosing as coprimary endpoints. Results.— The 2‐hour pain‐relief rate was significantly higher with almotriptan 25 mg compared with placebo (66.7% vs 55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2 hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and placebo groups was not significantly different. The 2‐hour pain‐relief rates (unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = .028, respectively). Rates for sustained pain relief also were significantly greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than with placebo group (52.4%), P < .01 for the 6.25‐ and 12.5‐mg doses and P < .05 for the 25‐mg dose. Age group subanalysis demonstrated significantly greater 2‐hour pain‐relief rates with all 3 doses of almotriptan compared with placebo for patients aged 15 to 17 years, a significantly lower incidence of photophobia and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for patients aged 15 to 17 years, and a significantly lower incidence of photophobia with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years. Almotriptan treatment was well tolerated, with the most common adverse events (>2%) of nausea, dizziness, and somnolence. Conclusions.— Oral almotriptan was efficacious for relieving migraine headache pain in adolescents, with the 12.5‐mg dose associated with the most favorable efficacy profile with respect to relieving headache pain and associated symptoms of migraine (photophobia and phonophobia). Almotriptan treatment was well tolerated in this adolescent population.     

Within-patient early versus delayed treatment of migraine attacks with almotriptan: the sooner the better

BACKGROUND: Migraine sufferers typically have been instructed to delay triptan therapy until headache intensity is at least moderate. Recent data suggest that earlier use of triptans may be more beneficial. OBJECTIVE: To address the potential "within-patient" benefit of intervention with almotriptan 12.5 mg for migraine headache of mild intensity. METHODS: We performed a post hoc analysis of a subgroup of patients from a large, open-label, long-term clinical trial wherein 762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity. Specifically, we evaluated the efficacy and safety of treatment in those patients who had treated at least 3 "mild" attacks and 3 "moderate/severe" attacks, examining rates of pain-free status, use of rescue medication, early recurrence, and adverse events for the first 3 mild and the first 3 moderate/severe attacks treated. RESULTS: There were 118 migraineurs and 708 attacks available for analysis. At 1 hour following treatment, pain-free status was achieved in 47% of mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2 hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue medication was required in 8% of mild attacks and in 13% of moderate/severe attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and 33% for moderate/severe attacks (P<.01). There was no difference in the incidence of adverse events for mild versus moderate/severe attacks (6% versus 7%). CONCLUSION: These results support early intervention with oral triptan therapy. When used for mild intensity head pain, almotriptan 12.5 mg produced a significantly higher incidence of pain-free status at 1 and 2 hours and lower incidences of early headache recurrence or need for rescue medication.     

Effect of early intervention with almotriptan vs placebo on migraine-associated functional disability: results from the AEGIS Trial

OBJECTIVE: To investigate the effect of early acute migraine intervention with almotriptan vs placebo on functional disability and health-related quality of life (HRQoL) indicators. DESIGN/METHODS: In this multicenter, double-blind, parallel-group trial, adults with international classification of headache disorders-defined migraine, with or without aura, were randomized 1:1 to treat 3 consecutive headaches with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of migraine headache pain of any intensity, within 1 hour of onset. Patients recorded level of functional disability (normal, disturbed, bed rest required, emergency room [ER]/hospitalization required) at baseline (pretreatment), 0.5, 1, 2, 4, and 24 hours posttreatment and at time of pain-free. Patients completed the Migraine Disability Assessment Scale (MIDAS) at randomization and completed the Migraine Quality-of-Life Questionnaire (MQoL) at 24 hours after each attack. RESULTS: Results are presented for 315 patients (160 almotriptan, 155 placebo) in the evaluable for efficacy population. At 2 hours posttreatment of Attack 1, 54.4%, 32.5%, 13.1%, and 0%, respectively, of almotriptan-treated patients reported normal function, disturbed function, bed rest required, and ER/hospitalization required compared with 38.1%, 45.2%, 16.1%, and 0.6%, respectively, of placebo-treated patients. The differences in level of functional disability between the 2 treatment groups were statistically significant at 2 hours (P = .007; Cochran-Mantel-Haenszel, stratified by center) and at 4 hours (P < .001). Resolution of pain was associated with a normal level of function; at 2 hours posttreatment, 91.7% of patients in the total population who achieved pain-free reported normal function compared with 44.8%, 8.0%, and 0% of patients with mild, moderate, and severe pain, respectively. The absence compared with the presence of photophobia, phonophobia, and nausea at 2 hours also was associated with less disability (P < .0001 for each symptom). Treatment with almotriptan compared with placebo resulted in consistently better 24-hour MQoL scores with significant results for all 3 migraine headache attacks in the social function and feelings/concern domains. A logistic regression model determined that pretreatment functional level (P = .0117), pretreatment pain intensity (P = .0089), and pretreatment MIDAS score (P = .0152) were significant covariates of the proportion of patients who achieved normal function at 2 hours posttreatment. CONCLUSIONS: Early treatment with almotriptan within 1 hour of migraine pain onset significantly reduced levels of functional disability at 2 and 4 hours posttreatment compared with placebo. Consistency in improvement of HRQoL indicators was observed across 3 headaches treated.