Crossover Comparison of Rizatriptan 5 mg and 10 mg Versus Sumatriptan 25 mg and 50 mg in Migraine

Rizatriptan is a selective 5-HT_1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.     

Efficacy and Safety of Rizatriptan Versus Standard Care During Long-term Treatment for Migraine

Rizatriptan is a novel, selective 5-HT_1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46 000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior ( P <0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.     

Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group

Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.     

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies

OBJECTIVE: To examine the short- and long-term efficacy and tolerability of rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were conducted in patients aged 12 to 17 years. The first study was a randomized, double-blind, placebo-controlled, single-attack study followed by a randomized, 1-year, open-label extension. The second study was a randomized, 1-year, open-label study. In the single-attack study, patients treated a moderate or severe migraine headache and up to two recurrences with rizatriptan 5-mg tablets (n = 234) or placebo (n = 242). Patients were instructed to use the study medication only on nonschool days. Headache severity, associated symptoms, and functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial dose. In the 1-year studies, patients treated up to 6 migraine attacks per month with rizatriptan 5-mg tablets (n = 273), rizatriptan 5-mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was assessed by the patient at 2 hours after the initial dose. In all studies, the primary efficacy measure was pain relief at 2 hours post dose. RESULTS: In the single-attack study, the proportion of patients with pain relief at 2 hours was not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients than expected (about 30%) treated their migraine attacks on the weekend. Among these patients, the proportion with pain relief at 2 hours was significantly higher in the rizatriptan group than in the placebo group (74% vs. 58%, P = 0.022). In the multiple-attack studies, pain relief at 2 hours was achieved in significantly more attacks treated with rizatriptan 5-mg tablet (77%) or with rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was well tolerated in both the studies, with an adverse event profile not significantly different from that of placebo or standard care. CONCLUSIONS: Rizatriptan 5 mg was not more effective than placebo in the treatment of a single migraine attack in adolescents, but appeared to be more effective than standard care for treating multiple attacks occurring over 1 year in these patients. Rizatriptan 5 mg was well tolerated in adolescents during short-term and long-term use.     

Rizatriptan (MAXALT) for the Acute Treatment of Migraine and Migraine Recurrence. A Placebo-Controlled, Outpatient Study

Rizatriptan is a novel 5-HT_1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo ( P <0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the l0-mg dose preferred as it is more effective with a faster onset of action.     

Migraine treatment outcomes with rizatriptan in triptan-naive patients: a naturalistic study.

BACKGROUND: The 5-hydroxytryptamine(1B/1D) agonists, or triptans, are the newest class of drugs to become available for the acute treatment of migraine. The class currently includes sumatriptan, zolmitriptan, naratriptan, and rizatriptan. The efficacy of rizatriptan in the acute treatment of migraine has been established against placebo and other oral triptans in controlled comparative trials. OBJECTIVE: The US Migraine Assessment Protocol (USMAP) collected data on the use of rizatriptan in a naturalistic setting reflecting clinical practice. This paper presents results for patients enrolled in the USMAP study who had never taken a triptan before the study. METHODS: At enrollment, 216 patients completed a questionnaire describing their responses to their current nontriptan medications. They were then given specially packaged samples of 4 standard 10-mg rizatriptan tablets and 4 orally disintegrating 10-mg rizatriptan tablets (wafers) and were asked to take a different formulation for each of their next 2 attacks, the sequence to be at their discretion. Within approximately 24 hours after taking rizatriptan, patients were to call a toll-free number to report their responses to rizatriptan using an interactive voice-response system. RESULTS: Within 2 hours after initial dosing of rizatriptan, significantly more patients taking either the rizatriptan tablet or the rizatriptan wafer reported onset of pain relief, had become largely symptom free, and were able to resume usual activities compared with their baseline responses to nontriptans (P < 0.05). In addition, compared with their baseline responses to nontriptans, significantly more patients taking either rizatriptan formulation had mild or no pain 2 hours after dosing (P < 0.05). More than twice as many patients taking the rizatriptan tablets or wafers were either somewhat or very satisfied with the medication compared with their satisfaction with nontriptans (P < 0.05). CONCLUSIONS: In the naturalistic setting of this study, migraineurs who had not previously taken a triptan medication reported more rapid relief of pain, more effective pain relief, and more rapid resumption of normal activities when taking rizatriptan tablets or wafers than when taking a nontriptan medication. Patients dissatisfied with their current nontriptan migraine therapy may benefit from treatment with rizatriptan.     

Early treatment of migraine with rizatriptan: a placebo-controlled study

OBJECTIVE: To evaluate the efficacy of rizatriptan when administered early during a migraine attack. BACKGROUND: Several studies indicate that triptans are more efficacious when administered early during a migraine attack, when the pain is still mild. METHODS: One hundred and twelve rizatriptan-na?ve patients aged 20 to 64 years with a history of migraine with or without aura that progressively worsened when left untreated were instructed to treat a total of three migraine attacks with either rizatriptan 10 mg or placebo as early as possible during each attack. Seventy-four patients (68 women and 6 men) were assigned to use the active drug and 38 (35 women and 3 men) to placebo. The primary efficacy endpoint was pain-free response at 2 hours after administration of the study drug. Secondary efficacy measures were pain-free response at 1 hour and sustained pain-free response lasting between 2 and 24 hours. RESULTS: A total of 216 attacks were treated in the rizatriptan group and 109 in the placebo group. Pain-free response at 2 hours after early treatment was noted in 151 (70%) of attacks in the rizatriptan group and in 24 (22%) in the placebo group (P < .01). Pain-free response at 1 hour occurred in 97 (45%) and 9 (8%) attacks, respectively (P < .01). When the attacks were categorized by headache severity at the time of treatment, the pain-free response at 2 hours was higher for mild attacks than for moderate or severe attacks (P < .01). Sustained pain-free response after treatment was significantly higher for attacks treated with rizatriptan (60%) than for those treated with placebo (17%) (P < .001). Adverse events were observed in 62 patients in the rizatriptan group and 15 in the placebo group. Only 1 patient taking rizatriptan discontinued the study because of adverse events, and no serious adverse events were reported. CONCLUSIONS: Rizatriptan is significantly more likely than placebo to produce a pain-free response within 2 hours when the drug is administered early in the migraine attack, when pain is mild rather than moderate or severe.     

Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups

Rizatriptan is a novel, selective 5-HT1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46,000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior (P < 0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.     

Rizatriptan wafer–sublingual vs. placebo at the onset of acute migraine

Rizatriptan wafer is a 5HT_1B/1D agonist for use in the acute treatment of migraine. It is a freeze-fried formulation, approved for oral administration, which dissolves on the tongue and is swallowed with saliva. In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a randomized, double-blind, placebo-controlled, out-patient study involving 39 migraineurs. Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo. At 1 h, 50% of the patients receiving rizatriptan wafer and 50% of the patients receiving placebo experienced significant relief. Implications and potential reasons for a high placebo response are discussed.     

Rizatriptan in the treatment of migraine

Rizatriptan is a selective 5-hydroxytriptamine1B/1D receptor agonist that was launched in 1998 for the acute treatment of migraine in adults. Based on data from 6 large clinical trials in patients > or =18 years of age in whom migraine was diagnosed according to International Headache Society criteria, the marketed 10-mg and 5-mg oral doses of rizatriptan are effective in relieving headache pain and associated migraine symptoms. The 10-mg dose is more effective than the 5-mg dose. At 2 hours after dosing, up to 77% of patients taking rizatriptan 10 mg had pain relief compared with 37% of those taking placebo, up to 44% were completely pain free compared with 7% of those taking placebo, and up to 77% were free of nausea compared with 58% of those taking placebo (P < 0.05 for all 3 comparisons). Both doses of rizatriptan are generally well tolerated. In placebo-controlled studies involving treatment of a single migraine attack, the most common side effects (incidence > or =2%) occurred in <10% of patients, typically were transitory (2 to 3 hours), and were mild or moderate. Rizatriptan is an effective and well-tolerated acute treatment for 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.     

Real-world experiences in migraine therapy with rizatriptan

OBJECTIVE: To evaluate the effectiveness of rizatriptan for acute migraine treatment and patient satisfaction with the drug in usual clinical practice settings. BACKGROUND: Although rizatriptan has been shown to effectively relieve migraine symptoms in clinical trials, we wished to assess its utility in typical patient care settings. Design.-Multicenter, open-label design involving the patients of practicing clinicians. METHODS: Adult migraineurs treated two migraine attacks with either rizatriptan 10-mg standard tablets or rizatriptan 10-mg orally disintegrating tablets in a crossover manner. Participants had not taken rizatriptan previously and chose which formulation to take first. Patients reported their treatment experiences via an interactive voice response system approximately 24 hours after treatment. Prior migraine treatment experiences were reported by patients on a baseline questionnaire completed at participating clinics. We used conditional logistic regression analysis adjusted for treatment sequences to test the statistical significance of comparisons with results recorded on the baseline questionnaire. RESULTS: Of the 5388 patients enrolled, 3953 (73%) completed at least one follow-up and 3183 (59%) completed two follow-up reports. Patients reported the following outcomes for attacks treated with the rizatriptan tablet and orally disintegrating tablet formulations, respectively, compared with their prior responses to oral usual care medications (P <.05 in all comparisons with baseline data): onset of pain relief within 30 minutes postdose: 18% and 23% versus 16%; no or mild headache 2 hours postdose: 66% and 67% versus 37%; largely symptom-free within 2 hours postdose: 52% and 54% versus 35%; return to usual activities within 2 hours postdose: 50% and 51% versus 31%; and very or somewhat satisfied with treatment: 72% and 74% versus 53%. CONCLUSIONS: In this "real-world" setting involving a patient population selected by clinicians, rizatriptan appeared to offer better treatment outcomes than those from prior treatments with other oral migraine medications.     

Efficacy and safety of rizatriptan wafer for the acute treatment of migraine

Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h (p < 0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.     

Further evaluation of rizatriptan in menstrual migraine: retrospective analysis of long-term data

OBJECTIVE: To determine the long-term efficacy of oral rizatriptan 10-mg wafers in the treatment of menstrual migraine attacks. METHODS: Data from an extension study where patients with migraine used rizatriptan 10 mg to treat moderate or severe migraine attacks occurring over periods of up to 6 months were included in a retrospective analysis. Patients used a diary card to record details of each migraine attack and onset of menstruation. Attacks in women were classified as menstrual or nonmenstrual according to 3 time windows relative to onset of menstruation (day 0): -3 to +3 days (7-day window), -2 to + 2 days (5-day window), and 0 to +1 days (2-day window). The analysis looked at the efficacy of rizatriptan 10 mg by menstrual category of attack for each definition on three measures: pain relief at 2 hours (reduction of pain to mild or none), pain free at 2 hours, 24-hours sustained pain free (pain free at 2 hours with no headache recurrence and no use of additional medications from 2 to 24 hours). RESULTS: Ninety-five women used rizatriptan 10 mg to treat a total of 1,839 attacks. The percentage of menstrual attacks was 30% for the -3 to +3 days definition, 23% for the -2 to +2 days definition, and 11% for the 0 to +1 days definition. Rizatriptan 10 mg was equally effective in menstrual and nonmenstrual migraine attacks regardless of the definition used. For example, using the -3 to +3 days definition, 78% of menstrual migraine attacks were relieved at 2 hours after dosing compared with 78% of nonmenstrual attacks. Pain relief rates for the other definitions were as follows: -2 to +2 days, menstrual = 78%, nonmenstrual = 78%; 0 to +1 days, menstrual = 79%, and nonmenstrual = 78%. No differences between menstrual and nonmenstrual attacks were found for the 2-hour pain free and 24-hour sustained pain free measures for any of the three definitions. CONCLUSIONS: Rizatriptan 10-mg wafers were equally effective in the treatment of menstrual and nonmenstrual migraine attacks occurring over 6 months, regardless of the precise definition of menstrual association used and even when the outcome criteria were very stringent. These data provide further evidence that triptans are effective treatments for menstrual migraine.     

Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine

BACKGROUND: Some comparative trials of selective serotonin 1B/ID-agonists in migraine have reported -15% lower efficacy for sumatriptan tablets than that reported in placebo-controlled trials. OBJECTIVE: This study was designed to test the hypothesis that the encapsulation methods used to mask active drug may delay absorption of sumatriptan from dosing to 2 hours after dosing (the traditional end point in clinical trials of migraine treatment), an effect that may be enhanced by migraine-associated gastric stasis. METHODS: Two randomized, open-label, 2-way crossover trials were conducted to evaluate the absorption and bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome protocol SUM40268). Absorption was assessed by calculating the area under the plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and maximum plasma concentration. Data for the AUC from time zero to infinity and maximum plasma concentration were used to assess standard bioequivalence, which is considered to occur when the 90% CIs for the geometric mean treatment ratios (test/reference) fall between 0.8 and 1.25. RESULTS: Study 1 included 26 healthy subjects (73% men, 27% women; mean age, 39.1 years), and study 2 included 30 patients with migraine (67% women, 33% men; mean age, 42.7 years). Sumatriptan absorption was delayed with the encapsulated tablet compared with the conventional tablet 0 to 2 hours after dosing, particularly during a migraine. AUC2 values with encapsulated sumatriptan compared with the conventional tablet were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI, 0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was demonstrated in both healthy volunteers and patients experiencing a migraine. CONCLUSIONS: Encapsulation delayed absorption of sumatriptan 0 to 2 hours after dosing, particularly during a migraine. This delay in absorption of the encapsulated form may account for the lower efficacy of sumatriptan in some comparative studies.     

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.     

Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials

OBJECTIVE: This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. BACKGROUND: Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. METHODS: Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. RESULTS: In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). CONCLUSIONS: Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.     

Efficacy and Safety of Sumatriptan Tablets (25 mg, 50 mg, and 100 mg) in the Acute Treatment of Migraine: Defining the Optimum Doses of Oral Sumatriptan

That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N=1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior ( P <0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior ( P <0.05) to sumatiptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.     

Rizatriptan 10-mg wafer versus usual nontriptan therapy for migraine: analysis of return to function and patient preference

BACKGROUND: More than half of patients with migraine suffer moderate to severe functional disability during migraine attacks. OBJECTIVE: To compare effects on functional disability at 2 hours after treating a migraine with rizatriptan 10-mg wafer versus usual nontriptan therapy for triptan-na?ve patients with migraine. DESIGN: Open-label, prospective, two-attack study conducted at 111 neurology clinics. METHODS: Adult patients with migraine treated two migraine attacks, the first with their usual nontriptan therapy (nonsteroidal anti-inflammatory drugs, 57%; analgesics, 27%; or ergot derivatives, 16%) and the second with rizatriptan 10-mg wafer. Patients recorded pain intensity and functional disability at the start, and functional disability at 2 hours, as well as the time of return to normal function. RESULTS: A total of 1353 patients, 76% of them female, completed the study and were considered evaluable. During first and second migraine attacks, 55% and 63% of patients, respectively, reported severe disability or requiring bed rest. At 2 hours after treatment, the likelihood of experiencing any disability was more than five times greater after usual nontriptan therapy than after rizatriptan (odds ratio, 5.68; 95% confidence interval (CI), 4.66 to 6.94; P < .001). Rizatriptan was twice as likely to return patients to normal function than usual nontriptan therapy after adjusting for confounding factors (adjusted hazard ratio, 2.08; 95% CI, 1.92 to 2.25; P < .001). Assessed over all time points up to 6 hours, the speed of return to normal function was 52% faster after rizatriptan therapy (P < .001). Significantly more patients preferred rizatriptan than usual nontriptan therapy (78.8% vs. 21.2%; P < .001). The most common reasons cited for preference for rizatriptan were faster relief of headache pain and faster return to normal function. CONCLUSIONS: Patients in this study were more likely to experience a return to normal function at 2 hours after receiving rizatriptan than after their usual nontriptan therapy for migraine. The results of this study, using patient-oriented, clinically relevant endpoints such as functional disability and preference, will help to guide practitioners in making recommendations for acute migraine treatment.     

Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine

OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.