The efficacy of RELPAX in the acute treatment of migraines was evaluated
in eight randomized, double-blind placebo-controlled studies. All eight
studies used 40 mg. Seven studies evaluated an 80 mg dose and two studies
included a 20 mg dose.
In all eight studies, randomized patients treated their headaches as
outpatients. Seven studies enrolled adults and one study enrolled adolescents
(age 11 to 17). Patients treated in the seven adult studies were predominantly
female (85%) and Caucasian (94%) with a mean age of 40 years (range 18 to
78). In all studies, patients were instructed to treat a 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 2 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 post dose. In
the adult studies, a second dose of RELPAX Tablets or other medication was
allowed 2 to 24 hours after the initial treatment for both persistent and
recurrent headaches. The incidence and time to use of these additional treatments
were also recorded.
In the seven adult studies, the percentage of patients achieving headache
response 2 hours after treatment was significantly greater among patients
receiving RELPAX Tablets at all doses compared to those who received placebo.
The two hour response rates from these controlled clinical studies are summarized
in Table 1.
Table 1: Percentage of Patients with Headache Response (Mild or No
Headache) 2 Hours Following Treatment
Comparisons of the performance of different drugs based upon results
obtained in different clinical trials are never reliable. Because studies
are generally 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 within
2 hours following treatment is depicted in Figure 1.
Figure 1: Estimated Probability of Initial Headache Response Within
2 Hours*
*Figure 1 shows the Kaplan-Meier plot of probability
over time of obtaining headache response (no or mild pain) following treatment
with eletriptan. The plot is based on 7 placebo-controlled, outpatient trials
in adults providing evidence of efficacy (Studies 1 through 7). Patients
not achieving headache response or taking additional treatment prior to
2 hours were censored at 2 hours.
For patients with migraine-associated photophobia, phonophobia, and nausea
at baseline, there was a decreased incidence of these symptoms following
administration of RELPAX as compared to placebo.
Two 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 taking a second dose or other medications for migraine over the 24 hours
following the initial dose of study treatment is summarized in Figure 2.
Figure 2: Estimated Probability of Taking a Second Dose/Other Medication
Over the 24 Hours Following the First Dose*
*This Kaplan-Meier plot is based on data obtained
in 7 placebo-controlled trials in adults (Studies 1 through 7). Patients
were instructed to take a second dose of study medication as follows: a)
in the event of no response at 2 hours (studies 2 and 4-7) or at 4 hours
(study 3); b) in the event of headache recurrence within 24 hours (studies
2-7). Patients not using additional treatments were censored at 24 hours.
The plot includes both patients who had headache response at 2 hours and
those who had no response to the initial dose. It should be noted that the
protocols did not allow remedication within 2 hours post dose.
The efficacy of RELPAX was unaffected by the duration of attack; gender
or age of the patient; relationship to menses; or concomitant use of estrogen
replacement therapy/oral contraceptives or frequently used migraine prophylactic
drugs.
In a single study in adolescents (n=274), there were no statistically
significant differences between treatment groups. The headache response
rate at 2 hours was 57% for both RELPAX 40 mg Tablets and placebo.