Randomized, controlled trial of telcagepant for the acute treatment of migraine.

BACKGROUND: The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology. In this large phase 3 clinical trial, we sought to confirm the efficacy of telcagepant, the first orally bioavailable CGRP receptor antagonist. METHODS: Adults with migraine with or without aura (International Headache Society criteria) treated a moderate or severe attack with oral telcagepant 50 mg (n = 177), 150 mg (n = 381), 300 mg (n = 371), or placebo (n = 365) in a randomized, double-blind trial. The 5 co-primary endpoints were pain freedom, pain relief, and absence of photophobia, absence of phonophobia, and absence of nausea, all at 2 hours postdose. The key secondary endpoint was 2-24 hour sustained pain freedom. The prespecified primary efficacy analyses evaluated the 150 mg and 300 mg groups; the 50-mg group was included on an exploratory basis to further characterize the dose response but was not prespecified for analysis. Tolerability was assessed by adverse experience reports. RESULTS: Telcagepant 300 mg was more effective (p

Age effects on placebo response rates in clinical trials of acute agents for migraine: pooled analysis of rizatriptan trials in adults.

This study examined the effect of age on placebo response rates in rizatriptan trials in adults. Data from eight rizatriptan adult trials involving patients treating moderate/severe migraine attacks with rizatriptan 5 mg (N = 1819), rizatriptan 10 mg (N = 2046) or placebo (N = 1322) were pooled for post hoc analysis. Logistic regression was used to model 2-h pain relief (reduction to mild or none) and 2-h pain freedom rates by treatment groups. Older patients had lower placebo response rates than younger patients; the estimated odds ratio (older vs. younger) for a 10-year age increase was 0.83 for pain relief [95% confidence interval (CI) 0.75, 0.93] and 0.81 for pain freedom (95% CI 0.68, 0.97). The response proportion vs. age trend was flat for rizatriptan 5 mg and slightly increased for rizatriptan 10 mg. The treatment-by-age interaction was significant for pain relief (P < 0.001) and pain freedom (P = 0.001), suggesting an increasing trend of treatment advantage of rizatriptan over placebo as age increased. Age appeared to be an important predictor of placebo response rate in rizatriptan trials, with older patients being less likely to respond to placebo and more likely to respond to rizatriptan.

Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.

BACKGROUND: In animals, insulin-like growth factor-1 (IGF-1) increases clearance of beta-amyloid, a pathologic hallmark of Alzheimer disease (AD), from the CNS. Serum IGF-1 level decreases with age, and shows a further decrease in AD. We examined whether the growth hormone secretagogue MK-677 (ibutamoren mesylate), a potent inducer of IGF-1 secretion, slows the rate of progression of symptoms in patients with AD. METHODS: A double-blind, multicenter study was conducted in which 563 patients with mild to moderate AD were randomized to receive MK-677 25 mg or placebo daily for 12 months. Efficacy measures were mean change from baseline at month 12 on the Clinician's Interview Based Impression of Change with caregiver input (CIBIC-plus), the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating-sum of boxes (CDR-sob). RESULTS: A total of 416 patients completed treatment and assessments at 12 months. Administration of MK-677 25 mg resulted in a 60.1% increase in serum IGF-1 levels at 6 weeks and a 72.9% increase at 12 months. In mixed-effects models that included treatment, time (month), randomization strata (baseline MMSE score < or =20 vs >20), and interaction of treatment-by-time, there were no significant differences between the treatment groups on the CIBIC-plus or the mean change from baseline scores on the ADAS-Cog, ADCS-ADL, or CDR-sob scores over 12 months. CONCLUSION: Despite evidence of target engagement as indicated by an increase in serum insulin-like growth factor-1, the human growth hormone secretagogue MK-677 25 mg was ineffective at slowing the rate of progression of Alzheimer disease.

Modelling future capacity needs and spending on colonoscopy in the English bowel cancer screening programme.

BACKGROUND: Bowel cancer screening using faecal occult blood testing and colonoscopy is currently being rolled out across England. Guidelines recommend that people identified by colonoscopy as having intermediate- or high-risk bowel polyps be offered periodic surveillance colonoscopy because of their elevated risk of bowel cancer. We make projections of the likely year-on-year increase in volumes and spending on colonoscopy due to the screening and surveillance programmes. METHODS: We constructed a model based on current bowel cancer screening and surveillance guidelines using screening outcome measures taken from the second round of the English bowel screening pilot. This was then used to predict colonoscopy volumes and cost for a hypothetical population. RESULTS: For a hypothetical population of 500,000 people, with average deprivation and 66,956 subjects aged 60-74 years, the initial screening and surveillance round would be expected to detect 34 cancers at a cost of 394,157 pounds sterling. In the first 8 years, colonoscopy numbers will grow at a rate of 23 per year, most of which will be surveillance colonoscopies. Colonoscopy costs may grow by 11,808 pounds sterling yearly in the same period, representing a cost per eligible person of 2.86 pounds sterling initially, increasing by 0.13 pounds sterling every year. Sensitivity analyses suggest significant changes in these predictions if screening uptake changes by 20%. CONCLUSION: The model has been used to make projections for five primary care trusts within the South Central Strategic Health Authority. Results from the volume and cost projections can inform service planning and resource allocation at local levels for the implementation of the current and future bowel cancer screening programme.

Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine.

OBJECTIVE: To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine. METHODS: Randomized, double-blind, parallel-group, clinical trial with a two-stage, adaptive, dose-ranging design. Patients were allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50, 100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The primary endpoint was pain relief (reduction to mild or none) 2 hours after dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain relief at 24 hours. A prespecified, blinded, automated interim analysis was used to discontinue randomization to less effective doses. RESULTS: Per the adaptive study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were discontinued due to insufficient efficacy. For the remaining treatment groups, the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which compared the average 2-hour pain relief response proportion of the combined 300, 400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A generally similar efficacy pattern was seen for other endpoints. MK-0974 was generally well tolerated and there did not appear to be an increase in adverse events with increasing dose. CONCLUSIONS: The novel, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.

Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine.

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.

Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study.

BACKGROUND: Inflammatory mechanisms have been implicated in the pathogenesis of Alzheimer's disease (AD) and may be mediated via the cyclo-oxygenase-2 enzyme. This study sought to evaluate the effect of rofecoxib, a nonsteroidal anti-inflammatory drug that selectively inhibits cyclo-oxygenase-2, in slowing the progression of dementia in patients with established AD. METHODS: A double-blinded, multicenter trial was conducted in which 692 patients with mild or moderate AD aged 50 years or older were randomly assigned to receive 25 mg rofecoxib or placebo daily for 12 months. The key efficacy measures were mean change from baseline at month 12 on the cognitive subscale of the AD Assessment Scale (ADAS-cog) and score on the Clinician's Interview Based Impression of Change with caregiver input (CIBIC+). RESULTS: Four hundred eighty-one patients (70%) completed assessments and remained on treatment at 12 months. No significant differences between treatments were found on the mean change from baseline error score for the ADAS-cog (rofecoxib = 4.84; placebo = 5.44; difference = -0.60) or mean score on the CIBIC+ (rofecoxib = 4.90; placebo = 4.87; difference = 0.03) over 12 months. This result persisted after adjusting for severity of dementia at baseline, presence of the APOE-epsilon4 allele, and donepezil use. Secondary analyses did not reveal any significant differences on any other measures. CONCLUSION: The failure of selective cyclo-oxygenase-2 inhibition to slow the progression of AD may indicate either that the disease process is too advanced to modify in patients with established dementia or that cyclo-oxygenase-2 does not play a significant role in the pathogenesis of the disorder.

Sum of Pain Intensity Differences (SPID) in migraine trials. A comment based on four rizatriptan trials.

Sum of Pain Intensity Difference (SPID) is an outcome measure that summarizes treatment response over a clinically relevant period. SPID is widely reported in clinical trials of analgesics but has been little used in migraine trials. We compared SPID over 2 h with the standard migraine outcome measures of pain-free at 2 h and headache relief at 2 h using data from four published clinical trials of rizatriptan in migraine patients. In assessing treatment response (rizatriptan and sumatriptan versus placebo, rizatriptan versus sumatriptan, within-treatment dose effects), SPID usually yielded similar results to the more easily understood pain-free measure.

Comparison of rizatriptan and other triptans on stringent measures of efficacy.

OBJECTIVE: To compare the efficacy of oral rizatriptan 10 mg with oral doses of sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures. METHODS: Retrospective analysis of data from five randomized, placebo-controlled, double-masked clinical trials in which oral rizatriptan was directly compared with oral sumatriptan 100 mg (n = 772), 50 mg (n = 1116), 25 mg (n = 1183), naratriptan 2.5 mg (n = 413), and zolmitriptan 2.5 mg (n = 580) for the acute treatment of a moderate or severe migraine attack. OUTCOME MEASURES: Percentage of patients pain-free at 2 hours, symptom-free at 2 hours (no pain, nausea, photophobia, phonophobia, vomiting, or functional disability), 24-hour sustained pain-free (no headache at 2 hours, no recurrence, and no additional antimigraine medications for 24 hours). RESULTS: More patients taking rizatriptan 10 mg were pain-free at 2 hours than were patients taking sumatriptan 100 mg (40% vs 33%, p = 0.019), sumatriptan 50 mg (40% vs 35%, p = 0.009), sumatriptan 25 mg (38% vs 27%, p < 0.001), naratriptan 2.5 mg (45% vs 21%, p < 0.001), and zolmitriptan 2.5 mg (43% vs 36%, p = 0.041). More patients taking rizatriptan 10 mg were symptom-free at 2 hours than were patients taking sumatriptan 100 mg (31% vs 22%, p = 0.002), sumatriptan 50 mg (33% vs 28%, p = 0.003), sumatriptan 25 mg (33% vs 24%, p < 0.001), naratriptan 2.5 mg (30% vs 11%, p < 0.001), and zolmitriptan 2.5 mg (31% vs 24%, p = 0.042). More patients taking rizatriptan 10 mg had a 24-hour sustained pain-free response than did patients taking sumatriptan 100 mg (27% vs 23%, p = 0.112), sumatriptan 50 mg (30% vs 26%, p = 0.015), sumatriptan 25 mg (27% vs 20%, p = 0.005), naratriptan 2.5 mg (29% vs 17%, p = 0.004), and zolmitriptan 2.5 mg (32% vs 24%, p = 0.013). CONCLUSION: Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response.

Effect of rizatriptan and other triptans on the nausea symptom of migraine: a post hoc analysis.

OBJECTIVE: To compare the effects of oral rizatriptan, sumatriptan, naratriptan, and zolmitriptan on the relief and emergence of nausea during a migraine attack. METHODS: Data from five randomized, placebo-controlled, double-blind clinical trials in which oral rizatriptan 10 mg was directly compared with oral sumatriptan 100 mg (N = 772), 50 mg (N = 1168), 25 mg (N = 1180), naratriptan 2.5 mg (N = 406), or zolmitriptan 2.5 mg (N = 571) for the acute treatment of a migraine attack were retrospectively analyzed. Migraine was diagnosed according to International Headache Society criteria. Presence or absence of nausea was recorded at baseline and at 0.5, 1, 1.5, and 2 hours after dosing. The end points analyzed were relief of nausea in those who had it at baseline and emergence of nausea in those who were free of it at baseline. Treatments were compared using odds ratios estimated from logistic regression models at 2 hours, and averaged odds ratios for the first 2 hours posttreatment. RESULTS: Approximately 60% of patients in each treatment group had nausea at baseline. In those patients with nausea at baseline, significantly more patients treated with rizatriptan 10 mg were free of nausea at 2 hours compared with sumatriptan 100 mg (66% versus 58%, P =.043), sumatriptan 50 mg (68% versus 57%, P =.010), sumatriptan 25 mg (68% versus 59%, P =.017), and naratriptan 2.5 mg (59% versus 45%, P =.014). Averaging over the four posttreatment time points in the first 2 hours, significantly more patients treated with rizatriptan 10 mg were free of nausea compared with sumatriptan 100 mg (P =.004), sumatriptan 50 mg (P =.001), and naratriptan 2.5 mg (P =.015). No significant differences in nausea relief were seen between rizatriptan 10 mg and zolmitriptan 2.5 mg, either at 2 hours (65% versus 61%, P =.210) or over the first 2 hours (P =.781). Rates of treatment-emergent nausea at 2 hours ranged from 11% to 18% with placebo, from 5% to 13% with rizatriptan 10 mg, and from 10% to 20% with other comparator triptans. CONCLUSIONS: Oral rizatriptan 10 mg was more effective than oral sumatriptan and naratriptan at eliminating nausea within 2 hours in patients who had it at baseline. Rates of emergent nausea in patients who were free of it at baseline were low, and no consistent differences were observed between active treatments.

Long-term efficacy and tolerability of rizatriptan wafers in migraine.

CONTEXT: Rizatriptan is a selective 5-HT1B/1D receptor agonist for the acute treatment of migraine. It is available in a unique wafer formulation that dissolves rapidly in the mouth and can be taken without liquids, thereby offering patients a very convenient way to take treatment. OBJECTIVE: To investigate the long-term efficacy of rizatriptan 10-mg and 5-mg wafers in migraineurs. SETTING: 19 headache clinics in 5 countries. PATIENTS: 458 patients diagnosed with migraine according to International Headache Society criteria. DESIGN: 6-month, open-label, extension, which followed a double-blind, placebo-controlled study. INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatments for moderate or severe migraines: rizatriptan 10-mg wafer, rizatriptan 5-mg wafer, or "standard care" (usual migraine treatment -- eg, nonsteroidal anti-inflammatory drugs [NSAIDs], analgesics, other triptans). Patients randomized to rizatriptan were blinded to the dose. MAIN OUTCOME MEASURES: Headache severity (none, mild, moderate, severe) and adverse events were recorded on a diary card. RESULTS: 181 patients treated 3393 attacks with rizatriptan 10-mg wafer, 191 treated 3254 attacks with rizatriptan 5-mg wafer, and 86 treated 1582 attacks with standard care. The median number of treated attacks per patient was 16 for rizatriptan 10-mg wafer, 13 for rizatriptan 5-mg wafer, and 14 for standard care. The median patient on rizatriptan 10-mg wafer reported pain relief at 2 hours (reduction of headache from moderate or severe at baseline to mild or none) in 82% of attacks, vs 73% of attacks for standard care (odds ratio [95% confidence interval] = 1.63 [1.14, 2.34], P <.01) and 72% of attacks for rizatriptan 5-mg wafer (OR [95% CI] = 1.60 [1.23, 2.08], P <.001). The median patient on rizatriptan 10-mg wafer was pain free at 2 hours in 46% of attacks, vs 30% of attacks for standard care (OR [95% CI] = 1.50 [1.06, 2.12], P <.05) and 25% of attacks for rizatriptan 5-mg wafer (OR [95% CI] = 1.93 [1.50, 2.49], P <.001). All treatments were generally well tolerated. Compared with standard care, rizatriptan 5-mg wafer was associated with fewer specific adverse events of asthenia/fatigue, back pain, nausea, pharyngeal discomfort, upper respiratory infection, and vomiting (P values <.05), and, compared with rizatriptan 10-mg wafer, fewer overall drug-related adverse events (P <.05). CONCLUSIONS: Rizatriptan 10-mg wafer was more effective than standard care and rizatriptan 5-mg wafer for treating intermittent moderate or severe migraine attacks occurring over periods of up to 6 months. Rizatriptan wafers were well tolerated.

Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials.

Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n = 2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for the acute treatment of a migraine attack. Migraine was diagnosed according to International Headache Society criteria. Headache severity, associated migraine symptoms and functional disability were measured immediately before dosing and at 0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache after an initial response) was also recorded. In addition to conventional pain relief (reduction of moderate or severe headache to mild or none) and pain free measures, the analysis looked at the elimination of associated migraine symptoms and disability in patients who had symptoms or disability at baseline. Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability. The benefit was maintained over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18% for placebo (P < 0.001). Rizatriptan 10 mg was also more effective than rizatriptan 5 mg, with a significant superiority at 2 h on all measures except for elimination of nausea. The benefit was maintained over 24 h; 38% of patients on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg (P = 0.001).

Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans.

Highly selective inhibitors of cyclooxygenase-2, such as rofecoxib, are hypothesized to have an improved gastrointestinal tolerability and safety profile compared with non-selective NSAIDs, which inhibit cyclooxygenase-1 and cyclooxygenase-2 non-selectively. This paper reviews data from randomized, double-blind, placebo-controlled studies which investigated the effects of rofecoxib and NSAIDs on the human gastrointestinal tract. In healthy subjects, rofecoxib 25 mg and 50 mg daily had no effect on gastric mucosal prostaglandin synthesis, whilst naproxen 1000 mg daily caused a 70% reduction. Therapeutic doses of rofecoxib 25 mg and 50 mg daily did not increase intestinal permeability or faecal blood loss in healthy subjects, whereas increases in both measures were seen with indometacin 150 mg or ibuprofen 2400 mg. A supra-therapeutic dose of rofecoxib (250 mg) given daily for 7 days did not induce an increase in gastroduodenal erosions in healthy subjects, whilst increased numbers of erosions were found in subjects given ibuprofen 2400 mg or aspirin 2600 mg. The endoscopic findings in healthy subjects were confirmed in two 6-month clinical studies involving 1516 patients with osteoarthritis; the incidences of ulcers following rofecoxib 25 mg or 50 mg daily were similar to placebo and less than ibuprofen 2400 mg. The advantage of rofecoxib over NSAIDs in these studies appears to translate into clinically relevant benefits; an analysis of 5435 patients with osteoarthritis found a significantly lower incidence of gastrointestinal perforations, ulcers and bleeds in patients taking rofecoxib compared with patients taking NSAIDs. Overall, the findings from these studies suggest that, as a result of cyclooxygenase-1 sparing, rofecoxib is significantly less gastrotoxic than non-selective NSAIDs, and may not differ from placebo.

Rizatriptan: pharmacological differences from sumatriptan and clinical results.

Rizatriptan and sumatriptan are selective 5-HT(1B/1D) receptor agonists for theacute treatment of migraine. For oral formulations, the time to maximum plasma concentration is reached earlier with rizatriptan than with sumatriptan (1 h versus 2-2.5 h) and rizatriptan has greater bioavailability than sumatriptan (45% versus 15%). These pharmacological advantages appear to translate into a faster onset of action and a better overall response for oral rizatriptan versus oral sumatriptan. The two drugs have been directly compared in randomized, double-blind, placebo-controlled clinical trials of patients with moderate or severe migraine attacks. Rizatriptan 10 mg was generally superior to sumatriptan on a measure of time-to-pain-relief within 2 h, where pain relief was defined as a reduction of pain to mild or none (odds ratio for rizatriptan versus sumatriptan 100 mg = 1.21; odds ratios for rizatriptan 10 mg versus sumatriptan 50 mg = 1.14 and 1.10 in two studies). Rizatriptan 10 mg was also superior to sumatriptan on the International Headache Society recommended endpoint of the percentage of patients pain free at 2 h (40% for rizatriptan 10 mg, 33% for sumatriptan 100 mg, and 35% for sumatriptan 50 mg). Further advantages for rizatriptan were seen on stringent outcome measures of the percentage of patients who were completely free of all symptoms at 2 h, patient satisfaction with medication at 2 h, and 24-h sustained pain-free response. 5-HT(1B/1D) receptor agonists are contraindicated in patients with coronary artery disease because of their potential to cause vasoconstriction. In clinical trials which excluded such patients, rizatriptan and sumatriptan were both well-tolerated. The most common side-effects on both drugs occurred in <10% of patients and consisted of dizziness, drowsiness, and asthenia/fatigue. The adverse events were usually mild or moderate in severity and short-lasting.

Within-patient consistency of response of rizatriptan for treating migraine.

OBJECTIVE: To determine the within-patient consistency of response for rizatriptan, a 5-HT(1B/1D) receptor agonist for the acute treatment of migraine. METHODS: Post hoc analysis was performed on data from a randomized, double-blind, placebo-controlled clinical trial. Four hundred seventy-three patients with migraine diagnosed according to the criteria of the International Headache Society were randomly assigned to one of five sequence groups in which each patient was scheduled to treat four separate moderate or severe migraine attacks. Patients in four groups received 10 mg of rizatriptan for three of four attacks and placebo for the remaining attack; patients in the fifth group received 10 mg of rizatriptan for all four attacks. Headache severity, functional disability, and associated migraine symptoms were measured immediately before dosing and at regular intervals up to 4 hours after the dose. The analysis was based on efficacy at 2 hours after dosing, the last time point before escape medications were allowed. The percentages of patients who responded in a specified number of attacks after treatment with rizatriptan were calculated. The analysis was descriptive, and no formal statistical testing was performed. RESULTS: Of the evaluable patients who treated three migraine attacks with 10 mg of rizatriptan (with an additional interspersed placebo-treated attack in most patients), 216 of 252 (86%) had pain relief (reduction of pain to mild or none), 122 of 252 (48%) were pain free, 211 of 250 (84%) had no nausea, 163 of 251 (65%) had no photophobia, 182 of 252 (72%) had no phonophobia, 136 of 249 (55%) had no functional disability, and 233 of 252 (92%) had no need for escape medications at 2 hours after dosing in at least two of three attacks. CONCLUSION: The response to 10 mg of oral rizatriptan within individual patients was consistent over three attacks on a range of measures.