Naratriptan clinical studies
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Clinical Trials
The efficacy of naratriptan tablets in the acute treatment of migraine headaches was evaluated in 6 randomized, double-blind, placebo-controlled studies of which 4 used the recommended dosing regimen and were conducted as outpatient trials. Three of these studies enrolled adult patients who were predominantly female (86%) and Caucasian (96%) with a mean age of 41 (range: 18 to 65). One study enrolled adolescents with a mean age of 14 (range: 12 to 17). In the adolescent study, 54% of the patients were female and 89% were Caucasian. In all studies, patients were instructed to treat at least 1 moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 4 hours after dosing. Associated symptoms such as nausea, vomiting, photophobia, and phonophobia were also assessed. Maintenance of response was assessed for up to 24 hours postdose. A second dose of naratriptan tablets or other medication was allowed 4 to 24 hours after the initial treatment for recurrent headache. The frequency and time to use of these additional treatments were also determined.
In all 3 trials in adults utilizing the recommended dosage regimen and outpatient use, the percentage of patients achieving headache response 4 hours after treatment, the primary outcome measure, was significantly greater among patients receiving naratriptan compared to those who received placebo. In all studies, response to 2.5 mg was numerically greater than response to 1 mg and in the largest of the 3 studies, there was a statistically significant greater percentage of patients with headache response at 4 hours in the 2.5 mg group compared to the 1 mg group. The results are summarized in Table 1.
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In the single study in adolescents, there were no statistically significant differences between any of the treatment groups. The headache response rates at 4 hours (n) were 65% (n = 74), 67% (n = 78), and 64% (n = 70) for placebo, 1 mg, and 2.5 mg groups, respectively. Comparisons of drug performance based upon results obtained in different clinical trials are never reliable. Because studies are conducted at different times, with different samples of patients, by different investigators, employing different criteria and/or different interpretations of the same criteria, under different conditions (dose, dosing regimen, etc.), quantitative estimates of treatment response and the timing of response may be expected to vary considerably from study to study. The estimated probability of achieving an initial headache response in adults over the 4 hours following treatment is depicted in Figure 1.
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The figure shows the probability over time of obtaining headache response (no or mild pain) following treatment with naratriptan tablets. The averages displayed are based on pooled data from the 3 controlled clinical trials providing evidence of efficacy (Studies 1, 2, and 3). In this Kaplan-Meier plot, patients not achieving response within 240 minutes were censored at 240 minutes.
For patients with migraine-associated nausea, photophobia, and phonophobia at baseline, there was a lower incidence of these symptoms 4 hours following administration of 1- and 2.5-mg naratriptan tablets compared to placebo.
Four to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain relief in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2.
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Kaplan-Meier plot based on data obtained in the 3 controlled clinical trials (Studies 1, 2, and 3) providing evidence of efficacy with patients not using additional treatments censored at 24 hours. The plot also includes patients who had no response to the initial dose. Remedication was discouraged prior to 4 hours postdose.
There is no evidence that doses of 5 mg provide a greater effect than 2.5 mg. There was no evidence to suggest that treatment with naratriptan was associated with an increase in the severity or frequency of migraine attacks. The efficacy of naratriptan tablets was unaffected by presence of aura; gender, age, or weight of the patient; oral contraceptive use; or concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants). There was insufficient data to assess the impact of race on efficacy.[1]
References
Adapted from the FDA Package Insert.